Imidazolopyridines and methods of making and using the same

ABSTRACT

Compounds of formula I possess unexpectedly high affinity for Alk 5 and/or Alk 4, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including fibrotic disorders. In one embodiment, the invention features a compound of formula I:

This non-provisional application is a continuation application ofPCT/US2003/027721, filed on Sep. 5, 2003, which is acontinuation-in-part and claims benefit of priority of U.S. Provisionalapplication 60/408,812, filed Sep. 6, 2002. The entire disclosure ofeach of the aforementioned patent applications are incorporated hereinby reference.

BACKGROUND OF THE INVENTION

TGFβ (Transforming Growth Factor β) is a member of a large family ofdimeric polypeptide growth factors that includes activins, inhibins,bone morphogenetic proteins (BMPs), growth and differentiation factors(GDFs) and mullerian inhibiting substance (MIS). TGFβ exists in threeisoforms (TGFβ1, TGFβ2, and TGFβ3) and is present in most cells, alongwith its receptors. Each isoform is expressed in both a tissue-specificand developmentally regulated fashion. Each TGFβ isoform is synthesizedas a precursor protein that is cleaved intracellularly into a C-terminalregion (latency associated peptide (LAP)) and an N-terminal region knownas mature or active TGFβ. LAP is typically non-covalently associatedwith mature TGFβ prior to secretion from the cell. The LAP-TGFβ complexcannot bind to the TGFβ receptors and is not biologically active. TGFβis generally released (and activated) from the complex by a variety ofmechanisms including interaction with thrombospondin-1 or plasmin.

Following activation, TGFβ binds at high affinity to the type IIreceptor (TGFβRII), a constitutively active serine/threonine kinase. Theligand-bound type II receptor phosphorylates the TGFβ type I receptor(Alk 5) in a glycine/serine rich domain, which allows the type Ireceptor to recruit and phosphorylate downstream signaling molecules,Smad2 or Smad3. See, e.g., Huse, M. et al., Mol. Cell. 8: 671-682(2001). Phosphorylated Smad2 or Smad3 can then complex with Smad4, andthe entire hetero-Smad complex translocates to the nucleus and regulatestranscription of various TGFβ-responsive genes. See, e.g., Massagué, J.Ann. Rev. Biochem. Med. 67: 773 (1998).

Activins are also members of the TGFβ superfamily that are distinct fromTGFβ in that they are homo- or heterodimers of activin βa or βb.Activins signal in a similar manner to TGFβ that is, by binding to aconstitutive serine-threonine receptor kinase, activin type II receptor(ActRIIB), and activating a type I serine-threonine receptor, Alk 4, tophosphorylate Smad2 or Smad3. The consequent formation of a hetero-Smadcomplex with Smad4 also results in the activin-induced regulation ofgene transcription.

Indeed, TGFβ and related factors such as activin regulate a large arrayof cellular processes, e.g., cell cycle arrest in epithelial andhematopoietic cells, control of mesenchymal cell proliferation anddifferentiation, inflammatory cell recruitment, immunosuppression, woundhealing, and extracellular matrix production. See, e.g., Massagué, J.Ann. Rev. Cell. Biol. 6: 594-641 (1990); Roberts, A. B. and Sporn M. B.Peptide Growth Factors and Their Receptors, 95: 419-472 Berlin:Springer-Verlag (1990); Roberts, A. B. and Sporn M. B. Growth Factors8:1-9 (1993); and Alexandrow, M. G., Moses, H. L. Cancer Res. 55:1452-1457 (1995). Hyperactivity of TGFβ signaling pathway underlies manyhuman disorders (e.g., excess deposition of extracellular matrix, anabnormally high level of inflammatory responses, fibrotic disorders, andprogressive cancers). Similarly, activin signaling and overexpression ofactivin is linked to pathological disorders that involve extracellularmatrix accumulation and fibrosis (see, e.g., Matsuse, T. et al., Am. J.Respir. Cell Mol. Biol. 13: 17-24 (1995); Inoue, S. et al., Biochem.Biophys. Res. Comm. 205: 441-448 (1994); Matsuse, T. et al, Am. J.Pathol. 148: 707-713 (1996); De Bleser et al., Hepatology 26: 905-912(1997); Pawlowski, J. E., et al., J. Clin. Invest. 100: 639-648 (1997);Sugiyama, M. et al., Gastroenterology 114: 550-558 (1998); Munz, B. etal., EMBO J. 18: 5205-5215 (1999)) and inflammatory responses (see,e.g., Rosendahl, A. et al., Am. J. Repir. Cell Mol. Biol. 25: 60-68(2001)). Studies have shown that TGFβ and activin can actsynergistically to induce extracellular matrix (see, e.g., Sugiyama, M.et al., Gastroenterology 114: 550-558, (1998)). It is thereforedesirable to develop modulators (e.g., antagonists) to signaling pathwaycomponents of the TGFβ family to prevent/treat disorders related to themalfunctioning of this signaling pathway.

SUMMARY OF THEE INVENTION

Compounds of formula (I) are unexpectedly potent antagonists of the TGFβfamily type I receptors, Alk5 and/or Alk 4. Thus, compounds of formula(I) can be employed in the prevention and/or treatment of diseases suchas fibrosis (e.g., renal fibrosis, pulmonary fibrosis, and hepaticfibrosis), progressive cancers, or other diseases for which reduction ofTGFβ family signaling activity is desirable.

In one aspect, the invention features a compound of formula I:

Each of X₁, X₂, X₃, and X₄ is independently CR^(x) or N; provided thatonly two of X₁, X₂, X₃, and X₄ can be N simultaneously. Each of Y₁ andY₂ is independently CR^(y) or N; provided that at least one of Y₁ and Y₂must be N. Each R¹ is independently alkyl, alkenyl, alkynyl, alkoxy,acyl, halo, hydroxy, amino, nitro, cyano, guanadino, amidino, carboxy,sulfo, mercapto, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl,aminocarbonyl, alkylcarbonylamino, alkylsulfonylamino, alkoxycarbonyl,alkylcarbonyloxy, urea, thiourea, sulfamoyl, sulfamide, carbamoyl,cycloalkyl, cycloalkyloxy, cycloalkylsulfanyl, heterocycloalkyl,heterocycloalkyloxy, heterocycloalkylsulfanyl, aryl, aryloxy,arylsulfanyl, aroyl, heteroaryl, heteroaryloxy, heteroarylsulfanyl, orheteroaroyl. Each R² is independently alkyl, alkenyl, alkynyl, acyl,halo, hydroxy, —NH₂, —NH(alkyl), —N(alkyl)₂, —NH(cycloalkyl),—N(alkyl)(cyclocalkyl),

—NH(heterocycloalkyl), —NH(heteroaryl), —NH-alkyl-heterocycloalkyl,—NH-alkyl-heteroaryl, —NH(aralkyl), cycloalkyl, (cycloalkyl)alkyl, aryl,aralkyl, aroyl, heterocycloalkyl, (heterocycloalkyl)alkyl, heteroaryl,heteroaralkyl, heteroaroyl, nitro, cyano, guanadino, amidino, carboxy,sulfo, mercapto, alkoxy, cycloalkyloxy, (cycloalkyl)alkoxy, aryloxy,arylalkoxy, heterocycloalkyloxy, (heterocycloalkyl)alkoxy,heteroaryloxy, heteroarylalkoxy, alkylsulfanyl, cycloalkylsulfanyl,(cycloalkyl)alkylsulfanyl, arylsulfanyl, aralkylsulfanyl,heterocycloalkylsulfanyl, (heterocycloalkyl)alkylsulfanyl,heteroarylsulfanyl, heteroarylalkylsulfanyl, alkylsulfinyl,alkylsulfonyl, aminocarbonyl, aminosulfonyl, alkylcarbonylamino,cycloalkylcarbonylamino, (cycloalkyl)alkylcarbonylamino,arylcarbonylamino, aralkylcarbonylamino,(heterocycloalkyl)carbonylamino, (heterocycloalkyl)alkylcarbonylamino,heteroarylcarbonylamino, heteroaralkylcarbonylamino,alkoxycarbonylaminoalkylamino, (heteroaryl)arylcarbonylaminoalkylamino,heteroaralkylcarbonylaminoalkylamino,(heteroaryl)arylsulfonylaminoalkylcarbonylaminoalkylamino,arylsulfonylaminoalkylamino, alkoxycarbonyl, alkylcarbonyloxy, urea,thiourea, sulfamoyl, sulfamide, or carbamoyl. m is 0, 1, 2, 3, or 4;provided that when m≧2, two adjacent R¹ groups can join together to forma 4- to 8-membered optionally substituted cyclic moiety. n is 0, 1, 2,or 3; provided that when n≧2, two adjacent R² groups can join togetherto form a 4- to 8-membered optionally substituted cyclic moiety. Each ofR^(x) and R^(y) is independently hydrogen, alkyl, alkenyl, alkynyl,alkoxy, acyl, halo, hydroxy, amino, nitro, cyano, guanadino, amidino,carboxy, sulfo, mercapto, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl,cycloalkylcarbonyl, (cycloalkyl)alkylcarbonyl, aroyl, aralkylcarbonyl,heterocycloalkylcarbonyl, (heterocycloalkyl)acyl, heteroaroyl,(heteroaryl)acyl, aminocarbonyl, alkylcarbonylamino,(amino)aminocarbonyl, alkylsulfonylaminocarbonyl, alkylsulfonylamino,cycloalkylcarbonylamino, cycloalkylsulfonylamino,(cycloalkyl)alkylcarbonylamino, (cycloalkyl)alkylsulfonylamino,arylcarbonylamino, arylsulfonylamino, aralkylcarbonylamino,aralkylsulfonylamino, (heterocycloalkyl)carbonylamino,(heterocycloalkyl)sulfonylamino, (heterocycloalkyl)alkylcarbonylamino,(heterocycloalkyl)alkylsulfonylamino, heteroarylcarbonylamino,heteroarylsulfonylamino, heteroaralkylcarbonylamino,heteroaralkylsulfonylamino, (heteroaryl)arylcarbonylaminoalkylamino,heteroaralkylcarbonylaminoalkylamino,(heteroaryl)arylsulfonylaminoalkylcarbonylaminoalkylamino,arylsulfonylaminoalkylamino, alkoxycarbonyl, alkylcarbonyloxy, urea,thiourea, sulfamoyl, sulfamide, carbamoyl, cycloalkyl, cycloalkyloxy,cycloalkylsulfanyl, (cycloalkyl)alkyl, (cycloalkyl)alkoxy,(cycloalkyl)alkylsulfanyl, heterocycloalkyl, heterocycloalkyloxy,heterocycloalkylsulfanyl, (heterocycloalkyl)alkyl,(heterocycloalkyl)alkoxy, (heterocycloalkyl)alkylsulfanyl, aryl,aryloxy, arylsulfanyl, aralkyl, aralkyloxy, aralkylsulfanyl,arylalkenyl, arylalkynyl, heteroaryl, heteroaryloxy, heteroarylsulfanyl,heteroaralkyl, (heteroaryl)alkoxy, or (heteroaryl)alkylsulfanyl.

As defined above, when m≧2, two adjacent R¹ groups can join together toform a 4- to 8-membered optionally substituted cyclic moiety. That is,the 2-pyridyl ring can fuse with a 4- to 8-membered cyclic moiety toform a moiety such as 7H-[1]pyrindinyl, 6,7-dihydro-5H-[1]pyrindinyl,5,6,7,8-tetrahydro-quinolinyl, 5,7-dihydro-furo[3,4-b]pyridinyl, or3,4-dihydro-1H-thiopyrano[4,3-c]pyridinyl. The fused ring moiety can beoptionally substituted with one or more substituents such as alkyl(including carboxyalkyl, hydroxyalkyl, and haloalkyl such astrifluoromethyl; see definiton of “alkyl” below), alkenyl, alkynyl,cycloalkyl, heterocycloalkyl, alkoxy, aryl, heteroaryl, aryloxy,heteroaryloxy, aralkyloxy, heteroarylalkoxy, aroyl, heteroaroyl, amino,nitro, carboxy, alkoxycarbonyl, alkylcarbonyloxy, aminocarbonyl,alkylcarbonylamino, cycloalkylcarbonylamino,cycloalkyl-alkylcarbonylamino, arylcarbonylamino, aralkylcarbonylamino,heterocycloalkyl-carbonylamino, heterocycloalkyl-alkylcarbonylamino,heteroarylcarbonylamino, heteroaralkylcarbonylamino, cyano, halo,hydroxy, acyl, mercapto, alkylsulfanyl, sulfoxy, urea, thiourea,sulfamoyl, sulfamide, oxo, or carbamoyl.

Similarly, when n≧2, two adjacent R² groups can join together to form a4- to 8-membered optionally substituted cyclic moiety, thereby forming aring fused with the pyridyl or pyrimidinyl group. Some examples of sucha moiety are shown below:

The 4- to 8-membered cyclic moiety formed by two adjacent R² groups canbe optionally substituted with substituents such as alkyl (includingcarboxyalkyl, hydroxyalkyl, and haloalkyl such as trifluoromethyl; seedefiniton of “alkyl” below), alkenyl, alkynyl, cycloalkyl,heterocycloalkyl, alkoxy, aryl, heteroaryl, aryloxy, heteroaryloxy,aralkyloxy, heteroarylalkoxy, aroyl, heteroaroyl, amino, nitro, carboxy,alkoxycarbonyl, alkylcarbonyloxy, aminocarbonyl, alkylcarbonylamino,cycloalkylcarbonylamino, cycloalkyl-alkylcarbonylamino,arylcarbonylamino, aralkylcarbonylamino, heterocycloalkyl-carbonylamino,heterocycloalkyl-alkylcarbonylamino, heteroarylcarbonylamino,heteroaralkylcarbonylamino, cyano, halo, hydroxy, acyl, mercapto,alkylsulfanyl, sulfoxy, urea, thiourea, sulfamoyl, sulfamide, oxo, orcarbamoyl.

In one embodiment, each of X₁, X₂, and X₃ is CR^(x). In one embodiment,each of X₂, X₃, and X₄ is independently —CH—, —C(CH₃)—, —C(OH)—,—C(NH₂)—, —C(CO—NH₂)—, —C(CO—NHOH)—, —C(NH(unsubstituted alkyl))-,—C(NH(aryl))-, —C(NH(aralkyl))-, —C(NH(heteroaryl))-,

—C(NH(heteroarylalkyl))-, —C(NH—CO-(unsubstituted alkyl))-,—C(NH—CO-(aryl))-, —C(NH—CO-(heteroaryl))-, —C(NH—CO-(aralkyl))-,—C(NH—CO-(heteroarylalkyl))-, —C(NH—SO₂-(unsubstituted alkyl))-,—C(NH—SO₂-(aryl))-, —C(NH—SO₂-(heteroaryl))-, —C(NH—SO₂-(aralkyl))-,—C(NH—SO₂-(heteroarylalkyl))-, —CNH—SO₂—NH(unsubstituted alkyl))-,—C(NH—SO₂—NH(aryl))-, —C(NH—SO₂—NH(heteroaryl))-,—C(NH—SO₂—NH(aralkyl))-, —C(NH—SO₂—NH(heteroarylalkyl))-,—C(hydroxyalkyl)-, or —C(carboxy)-, and X₁ is —CH—.

In one embodiment, each of X₁ and X₂ is —CH—; X₄ is N; and X₃ is—C(NH₂)—, —C(NH(unsubstituted alkyl))-, —C(NH(aryl))-, —C(NH(aralkyl))-,—C(NH(heteroaryl))-, —C(NH(heteroarylalkyl))-, —C(NH—CO-(unsubstitutedalkyl))-, —C(NH—CO-(aryl))-, —C(NH—CO-(heteroaryl))-,—C(NH—CO-(aralkyl))-, —C(NH—CO-(heteroarylalkyl))-,—C(H—SO₂-(unsubstituted alkyl))-, —C(NH—SO₂-(aryl))-,—C(NH—SO₂-(heteroaryl))-, —C(NH—SO₂-(aralkyl))-,—C(NH—SO₂-(heteroarylalkyl))-, —C(NH—SO₂—NH(unsubstituted alkyl))-,—CH—SO₂—NH(aryl))-,

—C(NH—SO₂—NH(heteroaryl))-, —C(NH—SO₂—NH(aralkyl))-, or—C(NH—SO₂—NH(heteroarylalkyl))-.

In one embodiment, both Y₁ are Y₂ are N.

In one embodiment, m is 0, 1, or 2 (e.g., m is 1). In one embodiment, R¹is substituted at the 5-position or the 6-position (i.e., R¹ can bemono-substituted at either the 5-position or the 6-position or R¹ can bedi-substituted at both the 5- and the 6-position). In one embodiment, R¹is C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkylthio, halo, amino, aminocarbonyl,or alkoxycarbonyl.

In one embodiment, n is 1 or 2 (e.g., n is 1).

In one embodiment, each R¹ is independently unsubstituted alkyl (e.g.,6-methyl, 6-ethyl, 6-n-propyl, or 6-isopropyl), hydroxyalkyl, haloalkyl(e.g., 6-trifluoromethyl), aminoalkyl, aryloxyalkyl,heteroaralkyloxyalkyl, unsubstituted alkenyl (e.g., 6-vinyl), alkoxy,acyl, halo, hydroxy, carboxy, cyano, guanadino, amidino, amino (e.g.,—NH₂, monoalkylamino, dialkylamino, monoheterocycloalkylamino,monoheteroarylamino, mono(heterocyclylalkyl)amino, mono(aralkyl)amino,or mono(heteroaralkyl)amino), carboxy, mercapto, alkylsulfanyl,alkylsulfinyl, alkylsulfonyl, aminocarbonyl (e.g., —CONH₂, —CONH(alkyl),or —CO—N(alkyl)₂), alkylcarbonylamino (e.g., —NH—CO-alkyl or—N(alkyl)-CO-alkyl), alkoxycarbonyl, alkylcarbonyloxy, alkylsulfonyl,sulfamoyl (e.g., —SO₂—NH₂, —SO₂—NH(alkyl), or —SO₂—N(alkyl)₂),cycloalkyl (e.g., 6-cyclopropyl), heterocycloalkyl,(heterocycloalkyl)alkyl, heteroaryl, or heteroaralkyl.

In one embodiment, each R² is independently unsubstituted alkyl,hydroxyalkyl, haloalkyl, aminoalkyl (e.g., aminomethyl), aryloxyalkyl,heteroaralkyloxyalkyl, alkoxy, acyl, halo, hydroxy, carboxy, cyano,guanadino, amidino, —NH₂, monoalkylamino, dialkylamino,monocycloalkylamino, monoheterocycloalkylamino (e.g., —NH-piperidinyl or—NH-morpholino), monoheteroarylamino (e.g., —NH-tetrazolyl,—NH-pyrazolyl, or —NH-imidazolyl), mono((heterocycloalkyl)alkyl)amino(e.g., —NH—(CH₂)₁₋₃-piperidinyl or —NH—(CH₂)₁₋₃-morpholino),mono(heteroaralkyl)amino (e.g., —NH—(CH₂)₁₋₃-tetrazolyl,—NH—(CH₂)₁₋₃-pyrazolyl, or —NH—(CH₂)₁₋₃-imidazolyl),—N(alkyl)(cycloalkyl), mercapto, alkylsulfanyl, alkylsulfinyl,alkylsulfonyl, —CONH₂, —CONH(alkyl), —CO—N(alkyl)₂, —NH—CO-alkyl,

—N(alkyl)-CO-alkyl, —CO₂-alkyl, —O—CO-alkyl, —SO₂—NH₂, —SO₂—NH(alkyl),—SO₂—N(alkyl)₂,

—NH—SO₂-alkyl, —N(alkyl)-SO₂-alkyl, —NH—CO—NH(alkyl),—N(alkyl)-CO—NH(alkyl), —NH—SO₂—NH(alkyl), —N(alkyl)-SO₂—NH(alkyl),heterocycloalkyl, or heteroaryl (e.g., imidazolyl, pyrazolyl,tetrazolyl, or pyridyl). For example, R² is substituted at the3-position and is guanadino, amidino, —NH₂, monoalkylamino,dialkylamino, monocycloalkylamino, monoheterocycloalkylamino,monoheteroarylamino, mono((heterocycloalkyl)alkyl)amino,mono(heteroaralkyl)amino, —NH—CO—NH(alkyl), —N(alkyl)-CO—NH(alkyl),—NH—SO₂—NH(alkyl), —N(alkyl)-SO₂—NH(alkyl), heterocycloalkyl, orheteroaryl.

In one embodiment, each R^(x) is independently hydrogen, unsubstitutedalkyl, hydroxyalkyl (e.g., hydroxy-C₁₋₄ alkyl such as hydroxyethyl),haloalkyl (e.g., trifluoromethyl), aminoalkyl, aryloxyalkyl,heteroaralkyloxyalkyl, alkoxy (e.g., C₁₋₄ alkoxy such as methoxy or C₁₋₄haloalkoxy such as —OCF₃), halo (e.g., chloro or bromo), hydroxy,carboxy, cyano, guanadino, amidino, amino (e.g., —NH₂, —NH(alkyl),—N(alkyl)₂,

—NH(heterocycloalkyl), —NH(heteroaryl), —NH(heterocycloalkyl-alkyl),—NH(aralkyl), or

—NH(heteroaralkyl)), carboxy, (heteroaryl)acyl, aminocarbonyl (e.g.,—CO—NH₂, —CO—NH—(CH₂)₀₋₃—COOH, —CO—NH—(CH₂)₀₋₃—OH,—CO—NH—(CH₂)₀₋₃-heteroaryl (e.g., —CO—NH—(CH₂)₀₋₃-tetrazolyl,—CO—NH—(CH₂)₀₋₃-pyrazolyl, or —CO—NH—(CH₂)₀₋₃-imidazolyl),—CO—NH—(CH₂)₀₋₃-heterocycloalkyl (e.g., —CO—NH—(CH₂)₀₋₃-piperidinyl or—CO—NH—(CH₂)₀₋₃-morpholino), or —CO—NH—(CH₂)₀₋₃-aryl (e.g.,—CO—NH—(CH₂)₀₋₃-phenyl), heteroarylcarbonylamino,(heterocycloalkyl)alkoxy, (heteroaryl)alkoxy, (heteroaryl)alkylsulfanyl,heterocycloalkyl (e.g., morpholino, pyrazinyl, or piperidinyl),(heterocycloalkyl)alkyl (e.g., morpholino-C₁₋₄ alkyl, pyrazinyl-C₁₋₄alkyl, or piperidinyl-C₁₋₄ alkyl), heteroaryl (e.g., imidazolyl,pyrazolyl, tetrazolyl, or pyridyl), or heteroaralkyl (e.g.,imidazolyl-C₁₋₄ alkyl, pyrazolyl-C₁₋₄ alkyl, tetrazolyl-C₁₋₄ alkyl, orpyridyl-C₁₋₄ alkyl). Some examples of —NH(alkyl) are

—NH(haloalkyl) (e.g., —NHCF₃), —NH(carboxyalkyl) (e.g.,—NH(CH₂)₁₋₃COOH), and —NH(hydroxyalkyl) (e.g., —NH(CH₂)₁₋₃OH). Someexamples of —NH(heteroaryl) are —NH(tetrazolyl), —NH(pyrazolyl), and—NH(imidazolyl). Some examples of —NH(heterocycloalkylalkyl) are—NH(piperazinylalkyl) (e.g., —NH(CH₂)₁₋₃-piperizine) and

—NH(morpholino-alkyl) (e.g., —NH(CH₂)₁₋₃-morpholine). Some examples of—NH(heteroaralkyl) are —NH(tetrazolylalkyl) (e.g.,—NH(CH₂)₀₋₃-tetrazole), —NH(pyrazolyl-alkyl) (e.g.,—NH(CH₂)₀₋₃-pyrazole), and —NH(imidazolyl-alkyl) (e.g.,—NH(CH₂)₀₋₃-imidazole).

In one embodiment, R^(y) is hydrogen, unsubstituted alkyl, hydroxyalkyl,haloalkyl (e.g., trifluoromethyl), aminoalkyl, aryloxyalkyl,heteroaralkyloxyalkyl, alkoxy, halo, hydroxy, carboxy, cyano, guanadino,amidino, amino (e.g., —NH₂, —NH(alkyl), —N(alkyl)₂, —NH(cycloalkyl),

—NH(heterocycloalkyl), —NH(heteroaryl), —NH(heterocycloalkyl-alkyl),—NH(aralkyl), or

—NH(heteroaralkyl)), carboxy, (heteroaryl)acyl, aminocarbonyl,heteroarylcarbonylamino, (heterocycloalkyl)alkoxy, (heteroaryl)alkoxy,(heteroaryl)alkylsulfanyl, heterocycloalkyl, (heterocycloalkyl)alkyl,heteroaryl, or heteroaralkyl.

In one embodiment, X₁ is N. For example, X₁ is N and each of X₂, X₃, andX₄ is independently CR^(x).

In one embodiment, X₂ is N. For example, X₂ is N and each of X₁, X₃, andX₄ is independently CR^(x).

In one embodiment, X₃ is N. For example, X₃ is N and each of X₁, X₂, andX₄ is independently CR^(x).

In one embodiment, X₄ is N. For example, X₄ is N and each of X₁, X₂, andX₃ is independently CR^(x).

Some examples of a compound of formula (I) are

-   (2-Methoxy-ethyl)-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine;-   (3-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-propyl)-carbamic    acid tert-butyl ester;-   (3-Imidazol-1-yl-propyl)-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine;-   (4-Methoxy-benzyl)-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine;-   [2-(6-Methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridin-6-yl]-methanol;-   3-(2-Methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine;-   (4-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butyl)-carbamic    acid tert-butyl ester;-   (4-Amino-benzyl)-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine;-   (5-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-pentyl)-carbamic    acid tert-butyl ester;-   [3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-6-yl]-methanol;-   [3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-7-yl]-methanol;-   [3-(2-Amino-pyrimidin-4-yl)-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-8-yl]-(2-morpholin-4-yl-ethyl)-amine;-   [3-(2-Amino-pyrimidin-4-yl)-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-8-yl]-(2-pyridin-2-yl-ethyl)-amine;-   [3-(2-Amino-pyrimidin-4-yl)-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-8-yl]-(2-pyridin-3-yl-ethyl)-amine;-   [3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-6-yl]-methanol;-   [3-(2-Amino-pyrimidin-4-yl)-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-8-yl]-(2-pyridin-4-yl-ethyl)-amine;-   [3-(2-Amino-pyrimidin-4-yl)-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-8-yl]-(3-morpholin-4-yl-propyl)-amine;-   [3-(4-Methyl-piperazin-1-yl)-propyl]-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine;-   [3-(4-Methyl-piperidin-1-yl)-propyl]-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine;-   [4-(2-Pyridin-2-yl-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-2-yl]-pyridin-3-ylmethyl-amine;-   {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-((R)-1-phenyl-ethyl)-amine;-   {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-((S)-1-phenyl-ethyl)-amine;-   {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(1H-tetrazol-5-yl)-amine;-   {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(2H-pyrazol-3-yl)-amine;-   {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(2-morpholin-4-yl-ethyl)-amine;-   {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(2-pyridin-2-yl-ethyl)-amine;-   {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(2-pyridin-3-yl-ethyl)-amine;-   {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(2-pyridin-4-yl-ethyl)-amine;-   {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(3-morpholin-4-yl-propyl)-amine;-   {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(3-piperidin-1-yl-propyl)-amine;-   {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-[1,3,4]thiadiazol-2-yl-amine;-   2-(6-Methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine;-   2-(6-Methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine-6-carboxylic    acid methyl ester;-   2-(6-Methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine-7-carboxylic    acid ethyl ester;-   2-(6-Methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-yl    amine;-   {7,7-Dimethyl-8-[5-(4-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butylcarbamoyl)-pentyl]-2-oxo-4-trifluoromethyl-7,8-dihydro-2H-1-oxa-8-aza-anthracen-5-yl}-methanesulfonic    acid;-   2-(2,7-Difluoro-6-hydroxy-3-oxo-9,9a-dihydro-3H-xanthen-9-yl)-3,5,6-trifluoro-4-[(4-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butylcarbamoyl)-methylsulfanyl]-benzoic    acid;-   2-(6-Methyl-pyridin-2-yl)-3-(2-morpholin-4-yl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine;-   2-(6-Methyl-pyridin-2-yl)-3-(2-piperidin-1-yl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine;-   2-(6-Methyl-pyridin-2-yl)-3-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine;-   2-(6-Methyl-pyridin-2-yl)-3-[2-(1H-tetrazol-5-yl)-pyrimidin-4-yl]-imidazo[1,2-a]pyridine;-   2-(6-Methyl-pyridin-2-yl)-3-pyrimidin-4-yl-imidazo[1,2-a]pyridine;-   2-(6-Methyl-pyridin-2-yl)-3-pyrimidin-4-yl-imidazo[1,2-a]pyrimidin-7-ylamine;-   3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-8-ylamine;-   3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carbonitrile;-   3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic    acid;-   3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic    acid ([1,4]dioxan-2-ylmethyl)-amide;-   3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic    acid ([1,4]dioxan-2-ylmethyl)-amide;-   3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic    acid (2-dimethylamino-ethyl)-amide;-   3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic    acid (2-methoxy-ethyl)-amide;-   3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic    acid (2-thiophen-2-yl-ethyl)-amide;-   3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic    acid [3-(4-methyl-piperazin-1-yl)-propyl]-amide;-   3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic    acid amide;-   3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic    acid cyclopropylamide;-   3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic    acid ethylamide;-   3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic    acid hydroxyamide;-   3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic    acid methoxy-amide;-   3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic    acid methyl ester;-   3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic    acid;-   3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic    acid ([1,4]dioxan-2-ylmethyl)-amide;-   3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic    acid (2-amino-ethyl)-amide;-   3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic    acid (2-dimethylamino-ethyl)-amide;-   3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic    acid (2-hydroxy-ethyl)-amide;-   3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic    acid (2-oxo-2-pyridin-3-yl-ethyl)-amide;-   3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic    acid (2-thiophen-2-yl-ethyl)-amide;-   3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic    acid (piperidin-3-ylmethyl)-amide;-   3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic    acid 2,2-dimethylhydrazide;-   3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic    acid amide;-   3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic    acid cyclopropylamide;-   3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic    acid ethyl ester;-   3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic    acid ethylamide;-   3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic    acid hydroxyamide;-   3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic    acid methoxy-amide;-   3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-ylamine;-   3-(2-Azetidin-1-yl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine;-   3-(2-Methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic    acid ethyl ester;-   3-(2-Methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic    acid methyl ester;-   3-(2-Methanesulfonyl-pyrimidin-4-yl)-7-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine;-   3-(2-Methanesulfonyl-pyrimidin-4-yl)-8-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine;-   3,3-Dimethyl-N-[2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-yl]-butyramide;-   3-(2-Methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carbonitrile;-   3-(2-Methylsulfanyl-pyrimidin-4-yl)-2-pyridin-2-yl-imidazo[1,2-a]pyridine;-   3,6-Dichloro-N-(4-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butyl)-2-(2,4,5,7-Tetrachloro-6-hydroxy-3-oxo-9,9a-dihydro-3H-xanthen-9-yl)-terephthalamic    acid;-   3-[2-(2-Methyl-aziridin-1-yl)-pyrimidin-4-yl]-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine;-   3-[2-(4-Methyl-piperazin-1-yl)-pyrimidin-4-yl]-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine;-   3-{[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carbonyl]-amino}-propionic    acid methyl ester;-   3-{[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carbonyl]-amino}-propionic    acid methyl ester;-   3-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-phenol;-   4-(2-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-ethyl)-benzenesulfonamide;-   4-(2-Pyridin-2-yl-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-2-ylamine;-   4-[2-(6-Chloro-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine;-   4-[2-(6-Methyl-pyridin-2-yl)-7-trifluoromethyl-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine;-   4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine;-   4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidine-2-carbonitrile;-   4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidine-2-carboxylic    acid amide;-   4-[6-Bromo-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine;-   4-[6-Chloro-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine;-   4-[6-Fluoro-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine;-   4-[6-Methyl-2-(6-methyl-pyridin-2-yl)-8-(2-morpholin-4-yl-ethylamino)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ol;-   4-[6-Methyl-2-(6-methyl-pyridin-2-yl)-8-(2-pyridin-2-yl-ethylamino)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ol;-   4-[6-Methyl-2-(6-methyl-pyridin-2-yl)-8-(2-pyridin-3-yl-ethylamino)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ol;-   4-[6-Methyl-2-(6-methyl-pyridin-2-yl)-8-(2-pyridin-4-yl-ethylamino)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ol;-   4-[6-Methyl-2-(6-methyl-pyridin-2-yl)-8-morpholin-4-yl-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ol;-   4-[6-Methyl-2-(6-methyl-pyridin-2-yl)-8-morpholin-4-yl-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine;-   4-[6-Methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine;-   4-[7-Aminomethyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine;-   4-[7-Methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine;-   4-[8-Benzyloxy-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ol;-   4-[8-Benzyloxy-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine;-   4-[8-Bromo-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ol;-   4-[8-Methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine;-   6-Chloro-3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine;-   5-Dimethylamino-naphthalene-1-sulfonic acid    (4-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butyl)-amide;-   6-(2,7-Difluoro-6-hydroxy-3-oxo-3H-xanthen-9-yl)-N-(4-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butyl)-isophthalamic    acid;-   6-Amino-9-[2-carboxy-5-(4-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butylcarbamoyl)-phenyl]-xanthen-3-ylidene-ammonium;-   6-Bromo-2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine;-   6-Fluoro-2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine;-   7-Amino-4-methyl-3-[(4-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butylcarbamoyl)-methyl]-2-oxo-2H-chromene-6-sulfonic    acid;-   Cyclobutyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl)-amine;-   Cyclopentyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine;-   Cyclopropyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine;-   Cyclopropyl-methyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine;-   Dimethyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine;-   Isopropyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine;-   Methyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine;-   N-(2-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-ethyl)-acetamide;-   N-(4-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butyl)-acetamide;-   N,N-Dimethyl-N′-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-ethane-1,2-diamine;-   N-[2-(6-Methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-yl]-3-pyridin-3-yl-propionamide;-   N-[2-(6-Methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-yl]-nicotinamide;-   N-[2-(6-Methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-yl]-propionamide;-   N-[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carbonyl]-methanesulfonamide;-   N-[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carbonyl]-methanesulfonamide;-   N-[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-2-(3-methoxy-phenyl)-acetamide;-   N-[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-3,3-dimethyl-butyramide;-   N-[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-3-pyridin-3-yl-propionamide;-   N-[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-acetamide;-   N-[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-nicotinamide;-   N-[3-(2-Methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-2-(3-methoxy-phenyl)-acetamide;-   N-[3-(2-Methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-3,3-dimethyl-butyramide;-   N-[3-(2-Methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-3-pyridin-3-yl-propionamide;-   N-[3-(2-Methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-nicotinamide;-   N-[3-(2-Methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-propionamide;-   N-[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-propionamide;-   N-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-acetamide;-   N1-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-butane-1,4-diamine;-   N1-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-propane-1,3-diamine;-   N-(4-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butyl)-(BODIPY    FL) amide; and-   N-(4-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butyl)-(Texas    Red-X) amide.

An N-oxide derivative or a pharmaceutically acceptable salt of each ofthe compounds of formula (I) is also within the scope of this invention.For example, a nitrogen ring atom of the imidazole core ring or anitrogen-containing heterocyclyl substituent can form an oxide in thepresence of a suitable oxidizing agent such as m-chloroperbenzoic acidor H₂O₂.

A compound of formula (I) that is acidic in nature (e.g., having acarboxyl or phenolic hydroxyl group) can form a pharmaceuticallyacceptable salt such as a sodium, potassium, calcium, or gold salt. Alsowithin the scope of the invention are salts formed with pharmaceuticallyacceptable amines such as ammonia, alkyl amines, hydroxyalkylamines, andN-methylglycamine. A compound of formula (I) can be treated with an acidto form acid addition salts. Examples of such an acid includehydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid,methanesulfonic acid, phosphoric acid, p-bromophenyl-sulfonic acid,carbonic acid, succinic acid, citric acid, benzoic acid, oxalic acid,malonic acid, salicylic acid, malic acid, fumaric acid, ascorbic acid,maleic acid, acetic acid, and other mineral and organic acids well knownto a skilled person in the art. The acid addition salts can be preparedby treating a compound of formula (I) in its free base form with asufficient amount of an acid (e.g., hydrochloric acid) to produce anacid addition salt (e.g., a hydrochloride salt). The acid addition saltcan be converted back to its free base form by treating the salt with asuitable dilute aqueous basic solution (e.g., sodium hydroxide, sodiumbicarbonate, potassium carbonate, or ammonia). Compounds of formula (I)can also be, e.g., in a form of achiral compounds, racemic mixtures,optically active compounds, pure diastereomers, or a mixture ofdiastereomers.

Compounds of formula (I) exhibit surprisingly high affinity to the TGFβfamily type I receptors, Alk 5 and/or Alk 4, e.g., with an IC₅₀ value ofless than 10 μM under conditions as described in Examples 7 and 8 below.Some compounds of formula (I) exhibit an IC₅₀ value of below 0.1 μM.

Compounds of formula (I) can also be modified by appending appropriatefunctionalities to enhance selective biological properties. Suchmodifications are known in the art and include those that increasebiological penetration into a given biological system (e.g., blood,lymphatic system, central nervous system), increase oral availability,increase solubility to allow administration by injection, altermetabolism, and/or alter rate of excretion. Examples of thesemodifications include, but are not limited to, esterification withpolyethylene glycols, derivatization with pivolates or fatty acidsubstituents, conversion to carbamates, hydroxylation of aromatic rings,and heteroatom-substitution in aromatic rings.

The present invention also features a pharmaceutical compositioncomprising a compound of formula (I) (or a combination of two or morecompounds of formula (I)) and a pharmaceutically acceptable carrier.Also included in the present invention is a medicament compositionincluding any of the compounds of formula (I), alone or in acombination, together with a suitable excipient.

The invention also features a method of inhibiting the TGFβ family typeI receptors, Alk 5 and/or Alk 4 (e.g., with an IC₅₀ value of less than10 μM; preferably, less than 1 μM; more preferably, less than 0.1 μM ina cell, including the step of contacting the cell with an effectiveamount of one or more compounds of formula (I). Also with the scope ofthe invention is a method of inhibiting the TGFβ and/or activinsignaling pathway in a cell or in a subject (e.g., a mammal such ashuman), including the step of contacting the cell with or administeringto the subject an effective amount of one or more of a compound offormula (I).

Also within the scope of the present invention is a method of treating asubject or preventing a subject from suffering a condition characterizedby or resulted from an elevated level of TGFβ and/or activin activity(e.g., from an overexpression of TGFβ). The method includes the step ofadministering to the subject an effective amount of one or more of acompound of formula (I). The conditions include an accumulation ofexcess extracellular matrix; a fibrotic condition (e.g., scleroderma,lupus nephritis, connective tissue disease, wound healing, surgicalscarring, spinal cord injury, CNS scarring, acute lung injury,idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease,adult respiratory distress syndrome, acute lung injury, drug-inducedlung injury, glomerulonephritis, diabetic nephropathy,hypertension-induced nephropathy, hepatic or biliary fibrosis, livercirrhosis, primary biliary cirrhosis, fatty liver disease, primarysclerosing cholangitis, restenosis, cardiac fibrosis, opthalmicscarring, fibrosclerosis, fibrotic cancers, fibroids, fibroma,fibroadenomas, fibrosarcomas, transplant arteriopathy, and keloid);demyelination of neurons multiple sclerosis; Alzheimer's disease;cerebral angiopathy; and TGFβ-induced metastasis of tumor cells andcarcinomas (e.g, squamous cell carcinomas, multiple myeloma, melanoma,glioma, glioblastomas, leukemia, and carcinomas of the lung, breast,ovary, cervix, liver, biliary tract, gastrointestinal tract, pancreas,prostate, and head and neck).

As used herein, an “alkyl” group refers to a saturated aliphatichydrocarbon group containing 1-8 (e.g., 1-6 or 1-4) carbon atoms. Analkyl group can be straight or branched. Examples of an alkyl groupinclude, but are not limited to, methyl, ethyl, propyl, isopropyl,butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-heptyl, and2-ethylhexyl. An alkyl group can be optionally substituted with one ormore substituents such as alkoxy, cycloalkyloxy, heterocycloalkyloxy,aryloxy, heteroaryloxy, aralkyloxy, heteroarylalkoxy, amino, nitro,carboxy, cyano, halo, hydroxy, sulfo, mercapto, alkylsulfanyl,alkylsulfinyl, alkylsulfonyl, aminocarbonyl, alkylcarbonylamino,cycloalkylcarbonylamino, cycloalkyl-alkylcarbonylamino,arylcarbonylamino, aralkylcarbonylamino, heterocycloalkyl-carbonylamino,heterocycloalkyl-alkylcarbonylamino, heteroarylcarbonylamino,heteroaralkylcarbonylamino, urea, thiourea, sulfamoyl, sulfamide,alkoxycarbonyl, or alkylcarbonyloxy.

As used herein, an “alkenyl” group refers to an aliphatic carbon groupthat contains 2-8 (e.g., 2-6 or 2-4) carbon atoms and at least onedouble bond. Like an alkyl group, an alkenyl group can be straight orbranched. Examples of an alkenyl group include, but are not limited to,allyl, isoprenyl, 2-butenyl, and 2-hexenyl. An alkenyl group can beoptionally substituted with one or more substituents such as alkoxy,cycloalkyloxy, heterocycloalkyloxy, aryloxy, heteroaryloxy, aralkyloxy,heteroarylalkoxy, amino, nitro, carboxy, cyano, halo, hydroxy, sulfo,mercapto, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, aminocarbonyl,alkylcarbonylamino, cycloalkylcarbonylamino,cycloalkyl-alkylcarbonylamino, arylcarbonylamino, aralkylcarbonylamino,heterocycloalkyl-carbonylamino, heterocycloalkyl-alkylcarbonylamino,heteroarylcarbonylamino, heteroaralkylcarbonylamino, urea, thiourea,sulfamoyl, sulfamide, alkoxycarbonyl, or alkylcarbonyloxy.

As used herein, an “alkynyl” group refers to an aliphatic carbon groupthat contains 2-8 (e.g., 2-6 or 2-4) carbon atoms and has at least onetriple bond. An alkynyl group can be straight or branched. Examples ofan alkynyl group include, but are not limited to, propargyl and butynyl.An alkynyl group can be optionally substituted with one or moresubstituents such as alkoxy, cycloalkyloxy, heterocycloalkyloxy,aryloxy, heteroaryloxy, aralkyloxy, heteroarylalkoxy, amino, nitro,carboxy, cyano, halo, hydroxy, sulfo, mercapto, alkylsulfanyl,alkylsulfinyl, alkylsulfonyl, aminocarbonyl, alkylcarbonylamino,cycloalkylcarbonylamino, cycloalkyl-alkylcarbonylamino,arylcarbonylamino, aralkylcarbonylamino, heterocycloalkyl-carbonylamino,heterocycloalkyl-alkylcarbonylamino, heteroarylcarbonylamino,heteroaralkylcarbonylamino, urea, thiourea, sulfamoyl, sulfamide,alkoxycarbonyl, or alkylcarbonyloxy.

As used herein, an “amino” group refers to —NR^(X)R^(Y) wherein each ofR^(X) and R^(Y) is independently hydrogen, hydroxyl, alkyl, alkoxy,cycloalkyl, (cycloalkyl)alkyl, aryl, aralkyl, heterocycloalkyl,(heterocycloalkyl)alkyl, heteroaryl, or heteroaralkyl. When the term“amino” is not the terminal group (e.g., alkylcarbonylamino), it isrepresented by —NR^(X)—. R^(X) has the same meaning as defined above.

As used herein, an “aryl” group refers to phenyl, naphthyl, or abenzofused group having 2 to 3 rings. For example, a benzofused groupincludes phenyl fused with one or two C₄₋₈ carbocyclic moieties, e.g.,1, 2, 3, 4-tetrahydronaphthyl, indanyl, or fluorenyl. An aryl isoptionally substituted with one or more substituents such as alkyl(including carboxyalkyl, hydroxyalkyl, and haloalkyl such astrifluoromethyl), alkenyl, alkynyl, cycloalkyl, (cycloalkyl)alkyl,heterocycloalkyl, (heterocycloalkyl)alkyl, aryl, heteroaryl, alkoxy,cycloalkyloxy, heterocycloalkyloxy, aryloxy, heteroaryloxy, aralkyloxy,heteroaralkyloxy, aroyl, heteroaroyl, amino, nitro, carboxy,alkoxycarbonyl, alkylcarbonyloxy, aminocarbonyl, alkylcarbonylamino,cycloalkylcarbonylamino, (cycloalkyl)alkylcarbonylamino,arylcarbonylamino, aralkylcarbonylamino,(heterocycloalkyl)carbonylamino, (heterocycloalkyl)alkylcarbonylamino,heteroarylcarbonylamino, heteroaralkylcarbonylamino, cyano, halo,hydroxy, acyl, mercapto, alkylsulfanyl, sulfoxy, urea, thiourea,sulfamoyl, sulfamide, oxo, or carbamoyl.

As used herein, an “aralkyl” group refers to an alkyl group (e.g., aC₁₋₄ alkyl group) that is substituted with an aryl group. Both “alkyl”and “aryl” have been defined above. An example of an aralkyl group isbenzyl.

As used herein, a “cycloalkyl” group refers to an aliphatic carbocyclicring of 3-10 (e.g., 4-8) carbon atoms. Examples of cycloalkyl groupsinclude cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, adamantyl,norbornyl, cubyl, octahydro-indenyl, decahydro-naphthyl,bicyclo[3.2.1]octyl, bicyclo[2.2.2]octyl, bicyclo[3.3.1]nonyl, andbicyclo[3.2.3]nonyl. A “cycloalkenyl” group, as used herein, refers to anon-aromatic carbocyclic ring of 3-10 (e.g., 4-8) carbon atoms havingone or more double bond. Examples of cycloalkenyl groups includecyclopentenyl, 1,4-cyclohexa-di-enyl, cycloheptenyl, cyclooctenyl,hexahydro-indenyl, octahydro-naphthyl, bicyclo[2.2.2]octenyl, andbicyclo[3.3.1]nonenyl. A cycloalkyl or cycloalkenyl group can beoptionally substituted with one or more substituents such as alkyl(including carboxyalkyl, hydroxyalkyl, and haloalkyl such astrifluoromethyl), alkenyl, alkynyl, cycloalkyl, (cycloalkyl)alkyl,heterocycloalkyl, (heterocycloalkyl)alkyl, aryl, heteroaryl, alkoxy,cycloalkyloxy, heterocycloalkyloxy, aryloxy, heteroaryloxy, aralkyloxy,heteroaralkyloxy, aroyl, heteroaroyl, amino, nitro, carboxy,alkoxycarbonyl, alkylcarbonyloxy, aminocarbonyl, alkylcarbonylamino,cycloalkylcarbonylamino, (cycloalkyl)alkylcarbonylamino,arylcarbonylamino, aralkylcarbonylamino, heterocycloalkyl-carbonylamino,(heterocycloalkyl)alkylcarbonylamino, heteroarylcarbonylamino,heteroaralkylcarbonylamino, cyano, halo, hydroxy, acyl, mercapto,alkylsulfanyl, sulfoxy, urea, thiourea, sulfamoyl, sulfamide, oxo, orcarbamoyl.

As used herein, a “heterocycloalkyl” group refers to a 3- to 10-membered(e.g., 4- to 8-membered) saturated ring structure, in which one or moreof the ring atoms is a heteroatom, e.g., N, O, or S. Examples of aheterocycloalkyl group include piperidinyl, piperazinyl,tetrahydropyranyl, tetrahydrofuryl, dioxolanyl, oxazolidinyl,isooxazolidinyl, morpholinyl, octahydro-benzofuryl, octahydro-chromenyl,octahydro-thiochromenyl, octahydro-indolyl, octahydro-pyrindinyl,decahydro-quinolinyl, octahydro-benzo[b]thiophenyl,2-oxa-bicyclo[2.2.2]octyl, 1-aza-bicyclo[2.2.2]octyl,3-aza-bicyclo[3.2.1]octyl, anad 2,6-dioxa-tricyclo[3.3.1.0^(3,7)]nonyl.A “heterocycloalkenyl” group, as used herein, refers to a 3- to10-membered (e.g., 4- to 8-membered) non-aromatic ring structure havingone or more double bonds, and wherein one or more of the ring atoms is aheteroatom, e.g., N, O, or S. A heterocycloalkyl or heterocycloalkenylgroup can be optionally substituted with one or more substituents suchas alkyl (including carboxyalkyl, hydroxyalkyl, and haloalkyl such astrifluoromethyl), alkenyl, alkynyl, cycloalkyl, (cycloalkyl)alkyl,heterocycloalkyl, (heterocycloalkyl)alkyl, aryl, heteroaryl, alkoxy,cycloalkyloxy, heterocycloalkyloxy, aryloxy, heteroaryloxy, aralkyloxy,heteroaralkyloxy, aroyl, heteroaroyl, amino, nitro, carboxy,alkoxycarbonyl, alkylcarbonyloxy, aminocarbonyl, alkylcarbonylamino,cycloalkylcarbonylamino, (cycloalkyl)alkylcarbonylamino,arylcarbonylamino, aralkylcarbonylamino, heterocycloalkyl-carbonylamino,(heterocycloalkyl)alkylcarbonylamino, heteroarylcarbonylamino,heteroaralkylcarbonylamino, cyano, halo, hydroxy, acyl, mercapto,alkylsulfanyl, sulfoxy, urea, thiourea, sulfamoyl, sulfamide, oxo, orcarbamoyl.

A “heteroaryl” group, as used herein, refers to a monocyclic, bicyclic,or tricyclic ring structure having 5 to 15 ring atoms wherein one ormore of the ring atoms is a heteroatom, e.g., N, O, S, or B and whereinone ore more rings of the bicyclic or tricyclic ring structure isaromatic. Some examples of heteroaryl are pyridyl, furyl, pyrrolyl,thienyl, thiazolyl, oxazolyl, imidazolyl, indolyl, tetrazolyl,benzofuryl, benzthiazolyl, xanthene, thioxanthene, phenothiazine,dihydroindole, and benzo[1,3]dioxole. A heteroaryl is optionallysubstituted with one or more substituents such as alkyl (includingcarboxyalkyl, hydroxyalkyl, and haloalkyl such as trifluoromethyl),alkenyl, alkynyl, cycloalkyl, (cycloalkyl)alkyl, heterocycloalkyl,(heterocycloalkyl)alkyl, aryl, heteroaryl, alkoxy, cycloalkyloxy,heterocycloalkyloxy, aryloxy, heteroaryloxy, aralkyloxy,heteroaralkyloxy, aroyl, heteroaroyl, amino, nitro, carboxy,alkoxycarbonyl, alkylcarbonyloxy, aminocarbonyl, alkylcarbonylamino,cycloalkylcarbonylamino, (cycloalkyl)alkylcarbonylamino,arylcarbonylamino, aralkylcarbonylamino, heterocycloalkyl-carbonylamino,(heterocycloalkyl)alkylcarbonylamino, heteroarylcarbonylamino,heteroaralkylcarbonylamino, cyano, halo, hydroxy, acyl, mercapto,alkylsulfanyl, sulfoxy, urea, thiourea, sulfamoyl, sulfamide, oxo, orcarbamoyl. A “heteroaralkyl” group, as used herein, refers to an alkylgroup (e.g., a C₁₋₄ alkyl group) that is substituted with a heteroarylgroup. Both “alkyl” and “heteroaryl” have been defined above.

As used herein, “cyclic moiety” includes cycloalkyl, heterocycloalkyl,cycloalkenyl, heterocycloalkenyl, aryl, or heteroaryl, each of which hasbeen defined previously.

As used herein, an “acyl” group refers to a formyl group or alkyl-C(═O)—where “alkyl” has been defined previously. Acetyl and pivaloyl areexamples of acyl groups.

As used herein, a “carbamoyl” group refers to a group having thestructure —O—CO—NR^(X)R^(Y) or —NR^(X)—CO—R^(Z) wherein R^(X) and R^(Y)have been defined above and R^(Z) is alkyl, cycloalkyl,(cycloalkyl)alkyl, aryl, aralkyl, heterocycloalkyl,(heterocycloalkyl)alkyl, heteroaryl, or heteroaralkyl.

As used herein, a “carboxy” and a “sulfo” group refer to —COOH and—SO₃H, respectively.

As used herein, an “alkoxy” group refers to an alkyl-O— group where“alkyl” has been defined previously.

As used herein, a “sulfoxy” group refers to —O—SO—R^(X) or —SO—R^(X),where R^(X) has been defined above.

As used herein, a “halogen” or “halo” group refers to fluorine,chlorine, bromine or iodine.

As used herein, a “sulfamoyl” group refers to the structure —S(O)₂—NRxRYor —NR^(X)—S(O)₂—R^(Z) wherein R^(X), R^(Y), and R^(Z) have been definedabove.

As used herein, a “sulfamide” group refers to the structure—NR^(X)—S(O)₂—NR^(Y)R^(Z) wherein R^(X), R^(Y), and R^(Z) have beendefined above.

As used herein, a “urea” group refers to the structure—NR^(X)—CO—NR^(Y)R^(Z) and a “thiourea” group refers to the structure—NR^(X)—CS—NR^(Y)R^(Z). R^(X), R^(Y), and R^(Z) have been defined above.

As used herein, an effective amount is defined as the amount which isrequired to confer a therapeutic effect on the treated patient, and istypically determined based on age, surface area, weight, and conditionof the patient. The interrelationship of dosages for animals and humans(based on milligrams per meter squared of body surface) is described byFreireich et al., Cancer Chemother. Rep., 50: 219 (1966). Body surfacearea may be approximately determined from height and weight of thepatient. See, e.g., Scientific Tables, Geigy Pharmaceuticals, Ardsley,N.Y., 537 (1970). As used herein, “patient” refers to a mammal,including a human.

An antagonist is a molecule that binds to the receptor withoutactivating the receptor. It competes with the endogenous ligand(s) orsubstrate(s) for binding site(s) on the receptor and, thus inhibits theability of the receptor to transduce an intracellular signal in responseto endogenous ligand binding.

As compounds of formula (I) are antagonists of TGFβ receptor type I(Alk5) and/or activin receptor type I (Alk4), these compounds are usefulin inhibiting the consequences of TGFβ and/or activin signaltransduction such as the production of extracellular matrix (e.g.,collagen and fibronectin), the differentiation of stromal cells tomyofibroblasts, and the stimulation of and migration of inflammatorycells. Thus, compounds of formula (I) inhibit pathological inflammatoryand fibrotic responses and possess the therapuetical utility of treatingand/or preventing disorders or diseases for which reduction of TGFβand/or activin activity is desirable (e.g., various types of fibrosis orprogressive cancers).

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. All publications, patentapplications, patents, and other references mentioned herein areincorporated by reference in their entirety. In addition, the materials,methods, and examples are illustrative only and not intended to belimiting.

Other features and advantages of the invention will be apparent from thefollowing detailed description, and from the claims.

DETAILED DESCRIPTION OF THE INVENTION

In general, the invention features compounds of formula (I), whichexhibit surprisingly high affinity for the TGFβ family type I receptors,Alk 5 and/or Alk 4.

Synthesis of Compounds of Formula (I)

Compounds of formula (I) may be prepared by a number of known methodsfrom commercially available or known starting materials. In one method,compounds of formula (I) are prepared according to Scheme 1 below.Specifically, a starting compound of formula (II) (where R² has beenselected beforehand) can be methylated in the presence of methyl iodideunder a basic condition (e.g., aq. NaOH) to yield form a compound offormula (III), which can be deprotonated under appropriate conditions(e.g., using sodium hexamethyldisilazane (NaHMS) in THF). Reaction ofthe deprotonated compound of formula (III) with a compound of formula(IV) (where R¹ has been selected beforehand) leads to an adduct compoundof formula (V). The adduct is then brominated and then cyclize with anamino-subsituted heterocycle of formula (VI) to yield a compound offormula (I).

Referring to Scheme 2 below, the thioether-substituted compound offormula (I) (see end product in Scheme 1) can be further modified toform other compounds of formula (I). Note that each of R^(A) and R^(B)represents hydrogen, alkyl, cycloalkyl, (cycloalkyl)alkyl, aryl,aralkyl, heterocycloalkyl, (heterocycloalkyl)alkyl, heteroaryl, orheteroaralkyl.

Alternatively, compounds of formula (I) can be prepared according toScheme 3 below. Specifically, a compound of formula (VII) can cyclizewith an amino-substituted heterocycle of formula (VI) to yield acompound of formula (VII), which can be brominated to form a compound offormula (IX). Compounds of formula (IX) and formula (X) can undergo aSuzuki coupling reaction to yield a compound of formula (I), which canbe further modified to form other compounds of formula (I). See theamination reaction as illustrated in the last step of Scheme 3 above(each of R^(A) and R^(B) having the same meaning as provided above). Forpreparation of a compound of formula (X), see WO 02/16359.

Alternatively, a bromo-substituted compound of formula (I) can bemodified to other compounds of formula (I) according to Scheme 4 below.

Alternatively, an amino-substituted compound of formula (I) can bemodified to other compounds of formula (I) according to Scheme 5 below,where R^(C) represents alkyl, cycloalkyl, (cycloalkyl)alkyl, aryl,aralkyl, heterocycloalkyl, (heterocycloalkyl)alkyl, heteroaryl, orheteroaralkyl.

It should be noted that the methods illustrated in Schemes above aremerely examples. One skilled in the art can easily modify these methodsto produce compounds of formula (I) other than those shown in theSchemes. For example, one can replace themono(methylsulfanyl)-substituted compound of formula (III) in Scheme 1with a di(methylsulfanyl)-substituted derivative (e.g.,4-methyl-2,6-bis-methylsulfanyl-pyrimidine, which can be preparedaccording to, e.g., Aust. J. Chem. 34:1729 (1981), Syn. Commun. 10:791(1980), or Synthesis 70-72 (1988)), thus resulting in variousdi-substituted compounds of formula (I) (i.e., disubstituted derivativesof compounds of formula (I) as shown in Schemes 1 and 2).

In one embodiment of the invention the molecular weight of the inventivecompound is no more than 1200. In another embodiment of the inventionthe molecular weight is no more than 1000.

As will be obvious to a skilled person in the art, some intermediatesmay need to be protected before undergoing synthetic steps as describedabove. For suitable protecting groups, see, e.g., T. W. Greene,Protective Groups in Organic Synthesis, John Wiley & Sons, Inc., NewYork (1981).

Uses of Compounds of Formula (I)

As discussed above, hyperactivity of the TGFβ family signaling pathwayscan result in excess deposition of extracellular matrix and increasedinflammatory responses, which can then lead to fibrosis in tissues andorgans (e.g., lung, kidney, and liver) and ultimately result in organfailure. See, e.g., Border, W. A. and Ruoslahti E. J. Clin. Invest.90:1-7 (1992) and Border, W. A. and Noble, N. A. N. Engl. J. Med. 331:1286-1292 (1994). Studies have been shown that the expression of TGFβand/or activin mRNA and the level of TGFβ and/or activin are increasedin patients suffering from various fibrotic disorders, e.g., fibrotickidney diseases, alcohol-induced and autoimmune hepatic fibrosis,myelofibrosis, bleomycin-induced pulmonary fibrosis, and idiopathicpulmonary fibrosis.

Compounds of formula (I), which are antagonists of the TGFβ family typeI receptors, Alk 5 and/or Alk 4, and inhibit TGFβ and/or activinsignaling pathway, are therefore useful for treating and/or preventingfibrotic disorders or diseases mediated by an increased level of TGFβand/or activin activity. As used herein, a compound inhibits the TGFβfamily signaling pathway when it binds (e.g., with an IC₅₀ value of lessthan 10 μM; preferably, less than 1 μM; more preferably, less than 0.1×to a receptor of the pathway (e.g., Alk 5 and/or Alk 4), therebycompeting with the endogenous ligand(s) or substrate(s) for bindingsite(s) on the receptor and reducing the ability of the receptor totransduce an intracellular signal in response to the endogenous ligandor substrate binding. The aforementioned disorders or diseases includeany conditions (a) marked by the presence of an abnormally high level ofTGFβ and/or activin; and/or (b) an excess accumulation of extracellularmatrix; and/or (c) an increased number and synthetic activity ofmyofibroblasts. These disorders or diseases include, but are not limitedto, fibrotic conditions such as scleroderma, idiopathic pulmonaryfibrosis, glomerulonephritis, diabetic nephropathy, lupus nephritis,hypertension-induced nephropathy, ocular or corneal scarring, hepatic orbiliary fibrosis, acute lung injury, pulmonary fibrosis, post-infarctioncardiac fibrosis, fibrosclerosis, fibrotic cancers, fibroids, fibroma,fibroadenomas, and fibrosarcomas. Other fibrotic conditions for whichpreventive treatment with compounds of formula (I) can have therapeuticutility include radiation therapy-induced fibrosis, chemotherapy-inducedfibrosis, surgically induced scarring including surgical adhesions,laminectomy, and coronary restenosis.

Increased TGFβ activity is also found to manifest in patients withprogressive cancers. Studies have shown that in late stages of variouscancers, both the tumor cells and the stromal cells within the tumorsgenerally overexpress TGFβ. This leads to stimulation of angiogenesisand cell motility, suppression of the immune system, and increasedinteraction of tumor cells with the extracellular matrix. See, e.g.,Hojo, M. et al., Nature 397: 530-534 (1999). As a result, the tumorscells become more invasive and metastasize to distant organs. See, e.g.,Maehara, Y. et al., J. Clin. Oncol. 17: 607-614 (1999) and Picon, A. etal., Cancer Epidemiol. Biomarkers Prev. 7: 497-504 (1998). Thus,compounds of formula (I), which are antagonists of the TGFβ type Ireceptor and inhibit TGFβ signaling pathway, are also useful fortreating and/or preventing various late stage cancers which overexpressTGFβ. Such late stage cancers include carcinomas of the lung, breast,liver, biliary tract, gastrointestinal tract, head and neck, pancreas,prostate, cervix as well as multiple myeloma, melanoma, glioma, andglioblastomas.

Importantly, it should be pointed out that because of the chronic and insome cases localized nature of disorders or diseases mediated byoverexpression of TGFβ and/or activin (e.g., fibrosis or cancers), smallmolecule treatments (such as treatment disclosed in the presentinvention) are favored for long-term treatment.

Not only are compounds of formula (I) useful in treating disorders ordiseases mediated by high levels of TGFβ and/or activin activity, thesecompounds can also be used to prevent the same disorders or diseases. Itis known that polymorphisms leading to increased TGFβ and/or activinproduction have been associated with fibrosis and hypertension. Indeed,high serum TGFβ levels are correlated with the development of fibrosisin patients with breast cancer who have received radiation therapy,chronic graft-versus-host-disease, idiopathic interstitial pneumonitis,veno-occlusive disease in transplant recipients, and peritoneal fibrosisin patients undergoing continuous ambulatory peritoneal dialysis. Thus,the levels of TGFβ and/or activin in serum and of TGFβ and/or activinmRNA in tissue can be measured and used as diagnostic or prognosticmarkers for disorders or diseases mediated by overexpression of TGFβand/or activin, and polymorphisms in the gene for TGFβ that determinethe production of TGFβ and/or activin can also be used in predictingsusceptibility to disorders or diseases. See, e.g., Blobe, G. C. et al.,N. Engl. J. Med. 342(18): 1350-1358 (2000); Matsuse, T. et al., Am. J.Respir. Cell Mol. Biol. 13: 17-24 (1995); Inoue, S. et al., Biochem.Biophys. Res. Comm. 205: 441-448 (1994); Matsuse, T. et al, Am. J.Pathol. 148: 707-713 (1996); De Bleser et al., Hepatology 26: 905-912(1997); Pawlowski, J. E., et al., J. Clin. Invest. 100: 639-648 (1997);and Sugiyama, M. et al., Gastroenterology 114: 550-558 (1998).

Administration of Compounds of Formula (I)

As defined above, an effective amount is the amount which is required toconfer a therapeutic effect on the treated patient. For a compound offormula (I), an effective amount can range from about 1 mg/kg to about150 mg/kg (e.g., from about 1 mg/kg to about 100 mg/kg). Effective doseswill also vary, as recognized by those skilled in the art, dependant onroute of administration, excipient usage, and the possibility ofco-usage with other therapeutic treatments including use of othertherapeutic agents and/or radiation therapy.

Compounds of formula (I) can be administered in any manner suitable forthe administration of pharmaceutical compounds, including, but notlimited to, pills, tablets, capsules, aerosols, suppositories, liquidformulations for ingestion or injection or for use as eye or ear drops,dietary supplements, and topical preparations. The pharmaceuticallyacceptable compositions include aqueous solutions of the active agent,in a isotonic saline, 5% glucose or other well-known pharmaceuticallyacceptable excipient. Solubilizing agents such as cyclodextrins, orother solubilizing agents well-known to those familiar with the art, canbe utilized as pharmaceutical excipients for delivery of the therapeuticcompounds. As to route of administration, the compositions can beadministered orally, intranasally, transdermally, intradermally,vaginally, intraaurally, intraocularly, buccally, rectally,transmucosally, or via inhalation, implantation (e.g., surgically), orintravenous administration. The compositions can be administered to ananimal (e.g., a mammal such as a human, non-human primate, horse, dog,cow, pig, sheep, goat, cat, mouse, rat, guinea pig, rabbit, hamster,gerbil, ferret, lizard, reptile, or bird).

Optionally, compounds of formula (I) can be administered in conjunctionwith one or more other agents that inhibit the TGFβ signaling pathway ortreat the corresponding pathological disorders (e.g., fibrosis orprogressive cancers) by way of a different mechanism of action. Examplesof these agents include angiotensin converting enzyme inhibitors,nonsteroid, steroid anti-inflammatory agents, and chemotherapeutics orradiation, as well as agents that antagonize ligand binding oractivation of the TGFβ receptors, e.g., anti-TGFβ, anti-TGFβ receptorantibodies, or antagonists of the TGFβ type II receptors.

The invention will be further described in the following examples, whichdo not limit the scope of the invention described in the claims.

EXAMPLE 12-(6-Methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine

Synthesis of the title compound is described in parts (a)-(c) below.

(a) 4-Methyl-2-methylsulfanyl-pyrimidine

Crushed sodium hydroxide (272.7 mmol) was added to a slurry of2-mercapto-4-methylpyrimidine HCl (122.8 mmol) in water (175 mL) at roomtemperature. After 15 minutes, iodomethane (134.9 mmol) was addeddropwise to the dark brown solution with formation of an orangeprecipitate. The slurry was stirred at room temperature for 3.5 hoursand then extracted with methylene chloride (3×60 mL). The combinedorganic phases were dried (Na₂SO₄) and concentrated in vacuo to give17.141 g of a dark brown oil identified as4-methyl-2-methylsulfanyl-pyrimidine. ¹H NMR (CDCl₃, 300 MHz): 2.41 (s,3H), 2.52 (s, 3H), 6.77 (d, J=5.06 Hz, 1H), 8.32 (d, J=5.12 Hz, 1H); MS(ESP+) 141.14 (M+1).

(b)1-(6-Methyl-pyridin-2-yl)-2-(2-methylsulfanyl-pyrimidin-4-yl)-ethanone

Sodium bis(trimethylsilyl)amide/THF (1.0 M, 74 mmol) was added dropwiseto a solution of 4-methyl-2-methylsulfanyl-pyrimidine (36.89 mmol) and6-methyl-pyridine-2-carboxylic acid ethyl ester (36.80 mmol) inanhydrous THF (74 mL) under a nitrogen atmosphere in a room temperaturewater bath. After stirring for 3 hours, the reaction was quenched withsaturated NH₄Cl (110 mL) and the organic and aqueous phases wereseparated. The aqueous phase was extracted with ethyl acetate (2×100mL). The combined organic phases were washed with water (100 mL) andbrine (100 mL), dried (MgSO₄), and concentrated in vacuo to give a darkorange solid, which was then slurried in ether at room temperature for 1hour, cooled at 0° C. overnight, filtered, and air dried to give 4.85 gof a dark brown solid identified as the enol of1-(6-methyl-pyridin-2-yl)-2-(2-methylsulfanyl-pyrimidin-4-yl)-ethanone.¹H NMR (CDCl₃, 400 MHz): 2.60 (s, 6H), 6.73 (s, 1H), 6.76 (d, J=5.35 Hz,1H), 7.17 (d, J=7.54 Hz, 1H), 7.67 (dd, J=7.72, 7.72 Hz, 1H), 7.75 (d,J=7.72 Hz, 1H), 8.33 (d, J=5.37 Hz, 1H), 14.30 (s, 1H); MS (ESP+) 260.16(M+1). The ether solution was concentrated it vacuo, dissolved in ethylacetate, treated with decolorizing carbon, filtered and concentrated invacuo to give a solid, which was slurried in ether at room temperaturefor 1 hour, cooled at 0° C. overnight, filtered, and air dried to give0.63 g of a light brown solid identified as a 4:1 mixture of theketone/enol form of1-(6-methyl-pyridin-2-yl)-2-(2-methylsulfanyl-pyrimidin-4-yl)-ethanone.

(c)2-(6-Methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine

Hydrogen bromide/acetic acid (30 wt %, 2.07 mmol) and 0.99 Mbromine/acetic acid (1.21 mmol) was added to a solution of1-(6-methyl-pyridin-2-yl)-2-(2-methylsulfanyl-pyrimidin-4-yl)-ethanone(0.89 mmol) and catalytic BHT in glacial acetic acid (4 mL) at roomtemperature to form a precipitate. After 1 hour of stirring, thereaction was diluted to 50 mL with ether, filtered, washed with ether,air dried briefly and then dissolved in ethanol (6 mL). The ethanolicsolution was added dropwise to a solution of 2-aminopyridine (0.965mmol) and diisopropylethylamine (2.67 mmol) in ethanol (1 mL) at 67° C.After stirring 3.5 hours, the reaction was concentrated in vacuo andpartioned between ether (20 mL) and 1 M HCl (10 mL). The aqueous phasewas washed with ether (2×10 mL), cooled in an ice bath and solid sodiumbicarbonate was added until the solution was neutral. The slurry wascooled at 0° C., filtered and air dried to give 0.18 g of brown solid,which was identified as the title compound,2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine.¹H NMR (CDCl₃, 300 MHz): 2.53 (s, 3H), 2.62 (s, 3H), 6.94 (dd, J=7.18,6.73 Hz, 1H), 7.14 (d, J=5.42 Hz, 1H), 7.18 (d, J=4.49 Hz, 1H), 7.36(dd, J=7.44, 8.35 Hz, 1H), 7.67 (d, J=4.43 Hz, 1H), 7.71 (dd, J=8.96 Hz,2H), 8.33 (d, J=5.38 Hz, 1H), 9.49 (d, J=7.09 Hz, 1H); MS (ESP+) 334.15(M+1).

EXAMPLE 23-(2-Methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine

Sulfuric acid (4.0 N, 0.04 mmol), catalytic sodium tungstate dihydrate,and 30 wt % hydrogen peroxide (1.01 mmol) was added to a slurry of2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine(0.31 mmol; see Example 1 for its preparation) in methanol (2 mL) at 55°C. All solids dissolved at the beginning of the reaction, then aprecipitate formed. After 3 hours of stirring, the reaction was dilutedwith water (2 mL) and warmed to 55° C. for a further 0.5 hour. Thereaction was then cooled to room temperature, quenched with saturatedsodium thiosulfate and concentrated in vacuo. The solid was partionedbetween ethyl acetate (20 mL) and water (10 mL). The organic phase waswashed with 2M sodium carbonate (7 mL) and brine (7 mL), dried (Na₂SO₄)and concentrated in vacuo to give 0.10 g of a yellow solid identified asthe title compound,3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine.¹H NMR (CDCl₃, 400 MHz): 2.54 (s, 3H), 3.39 (s, 3H), 7.12 (dd, J=6.93,7.76 Hz, 1H), 7.25 (d, J=7.61 Hz, 1H), 7.50 (dd, J=7.32, 7.67 Hz, 1H),7.77 (dd, J=7.73, 7.73 Hz, 1H), 7.83 (d, J=8.91 Hz, 1H), 7.89 (d, J=9.02Hz, 1H), 7.90 (d, J=5.58 Hz, 1H), 8.66 (d, J=5.55 Hz, 1H), 9.74 (d,J=7.08 Hz, 1H); MS (ESP+) 366.09 (M+1).

EXAMPLE 3(4-Methoxy-benzyl)-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine

A slurry of 4-methoxybenzylamine (0.54 mmol) and3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.27 mmol; see Example 2 for its preparation) in acetonitrile (1 mL)was warmed to reflux. After refluxing for 20 hours, 4-methoxybenzylamine(0.27 mmol) was added. After refluxing for an additional 4.5 hours, thereaction was allowed to cool to room temperature and concentrated invacuo to give a yellow solid. This solid was dissolved in chloroform (20mL), washed with 5% citric acid (6 mL), 10% sodium bicarbonate (6 mL)and brine (7 mL), dried (Na₂SO₄) and concentrated in vacuo to give 0.11g of a yellow wax, which was identified as the title compound,(4-methoxy-benzyl)-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine.¹H NMR (CDCl₃, 300 MHz): 2.57 (s, 3H), 3.82 (s, 3H), 4.65 (d, J=5.9 Hz,2H), 6.65 (d, J=5.3 Hz, 1H), 6.6-6.71 (br m, 1H), 6.89-6.94 (m, 2H),7.18 (br d, J=5.3 Hz, 1H), 7.25-7.28 (m, 2H), 7.31-7.36 (m, 2), 7.89 (brd, J=5.6 Hz, 1H), 7.93 (d, J=8.1 Hz, 1H), 7.97 (br d, J=9.6 Hz, 1H),8.13 (d, J=5.3 Hz, 1H), 9.16 (br s, 1H); MS (ESP+) 423.20 (M+1); MS(ESP−) 421.21 (M−1).

EXAMPLE 44-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine

A solution of(4-methoxy-benzyl)-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine(0.2627 mmol; see Example 3 for its preparation) in 1:1 dioxane/5N HCl(4 mL) was warmed to 100° C. for 2 days. The resultant solution was thenconcentrated in vacuo and purified by reverse phase HPLC(acetonitrile/water gradient with 0.1% TFA) to give 0.02 g of a yellowsolid, which was identified as the TFA salt of the title compound,4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine.¹H (d6-DMSO, 400 MHz): 2.48 (s, 3H), 6.75 (d, J=5.9 Hz, 1H), 7.20 (ddd,J=1.1, 6.9, 6.9 Hz, 1), 7.39 (d, J=7.7 Hz, 1H), 7.62 (ddd, J=1.1, 6.9,6.9 Hz, 1H), 7.77 (d, J=7.7 Hz, 1H), 7.83 (d, J=8.9 Hz, 1H), 7.89 (dd,J=7.7, 7.7 Hz, 1H), 8.18 (d, J=5.9 Hz, 1H), 9.59 (d, J=7 Hz, 1H); MS(ESP+) 303.11 (M+1).

EXAMPLE 53-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-ylamine

A solution of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-ylamine(0.0718 mmol; prepared in accordance with Example 2) and 28 wt %ammonium hydroxide (4.34 mmol) in dioxane (2 mL) was warmed to 100° C.in a sealed tube. After 19.5 hours, the reaction was concentrated invacuo and purified via reverse phase HPLC (acetonitrile/water gradientwith 0.1% TFA) to give 0.0200 g of a yellow solid identified as the TFAsalt of the title compound,3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-ylamine.¹H NMR (DMSO-d6, 400 MHz): 2.49 (s, 1.5H), 2.50 (s, 1.5H), 6.54 (d,J=5.37 Hz, 1H), 6.64 (d, J=7.71 Hz, 1H), 7.15 (br s, 2H), 7.40 (d,J=7.75 Hz, 1H), 7.55 (d, J=7.74 Hz, 1H), 7.84 (dd, J=7.79, 7.17 Hz, 1H),8.17 (d, J=5.37 Hz, 1H), 8.18 (br s, 2H), 9.32 (d, J=7.53 Hz, 1H); MS(ESP+) 319.18 (M+1).

EXAMPLE 62-(6-Methyl-pyridin-2-yl)-3-(2-morpholin-4-yl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine

A solution of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.121 mmol; see Example 2 for its preparation) and 4-aminomorpholine(0.38 mmol) in anhydrous acetonitrile (1 mL) was warmed to 100° C. in asealed tube. After 3 days, 4-aminomorpholine (0.76 mmol) was added andthe reaction warmed at 100° C. for an additional day. The reaction wasthen concentrated in vacuo and purified via reverse phase HPLC(water/acetonirile gradient with 0.1% TFA) to give 0.0258 g of an orangesolid identified as the TFA salt of the title compound,2-(6-methyl-pyridin-2-yl)-3-(2-morpholin-4-yl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine.¹H NMR (DMSO-d6, 400 MHz): 2.43 (s, 3H), 3.60-3.71 (m, 4), 6.75 (d,J=6.75 Hz, 1H), 7.16 (dd, J=6.79, 7.11 Hz, 1H), 7.37 (d, J=7.70 Hz, 1),7.57 (dd, J=7.57, 8.26 Hz, 1H), 7.70 (d, J=7.75 Hz, 1H), 7.77 (d, J=9.01Hz, 1H), 7.86 (dd, J=7.74, 7.78 Hz, 1H), 8.35 (d, J=5.12 Hz, 1H), 9.13(d, J=7.01 Hz, 1H); MS (ESP+) 373.19 (M+1).

EXAMPLE 7(4-Amino-benzyl)-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine

In a sealed tube, a solution of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.147 mmol; see Example 2 for its preparation) and4-aminomethyl-phenylamine (0.443 mmol) in CH₃CN (2 mL) was warmed atreflux overnight. The reaction was then concentrated in vacuo andpurified via preparatory HPLC (5→45% CH₃CN/H₂O with 0.1% TFA) to yield32 mg of(4-amino-benzyl)-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amineas the TFA salt. ¹H NMR (d₆-DMSO, 400 MHz): 2.58 (s, 3H), 4.58 (d, 2H,J=5.7 Hz), 6.72 (d, 1H, J=5.0 Hz), 7.19 (d, 2H, J=7.2 Hz), 7.42 (d, 2H,J=7.7 Hz), 7.57 (s, 1H), 7.78 (d, 1H, J=7.7 Hz), 7.82 (d, 1H, J=9.3 Hz),7.92 (d, 1H, 7.2 Hz), 8.16 (s, 1H), 8.29 (d, 1H, J=5.0 Hz); MS (ESP+)408.2 (M+1).

EXAMPLE 8{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(2-morpholin-4-yl-ethyl)-amine

In a sealed tube, a solution of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.147 mmol; see Example 2 for its preparation)) and2-morpholin-4-yl-ethyl amine (0.443 mmol) in CH₃CN (2 mL) aas warmedatat reflux overnight. The reaction was concentrated in vacuo andpurified via preparatory HPLC (5→50% CH₃CN/H₂O with 0.1% TFA) to yield34 mg of{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(2-morpholin-4-yl-ethyl)-amineas the TFA salt. ¹H NMR (d₆-DMSO, 400 MHz): 2.53 (s, 3H), 3.40 (m, 2H),3.42 (m, 4H), 3.75 (m, 2H), 3.91 (m, 4H), 6.85 (s, 1H), 7.20(ddd, 1H,J=0.7 Hz, 6.9, 6.9 Hz), 7.39 (d, 1H, J=7.5 Hz), 7.61 (m, 2H), 7.79 (d,1H, J=7.5 Hz), 7.84 (d, 1H, J=7.5 Hz), 7.91 (dd, 1H, J=7.6, 7.6 Hz),8.37 (d, 1H, J=4.8 Hz); MS (ESP+) 416.3 (M+1).

EXAMPLE 9N,N-Dimethyl-N′-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-ethane-1,2-diamine

In a sealed tube, a solution of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.192 mmol; see Example 2 for its preparation) andN,N-dimethylethyldiamine (0.574 mmol) in CH₃CN (2 mL) was warmed atreflux overnight. The reaction was concentrated in vacuo and purifiedvia preparatory HPLC (5→50% CH₃CN/H₂O with 0.1% TFA) to yield 10 mg ofN,N-dimethyl-N′-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-ethane-1,2-diamineasthe TFA salt. ¹H NMR (d₆-DMSO, 400 MHz): 2.51 (s, 3H), 2.89 (d, 6×3.6Hz), 3.35 (ddd, 2H, J=6.0, 5.7, 5.7 Hz), 3.72 (ddd, 2H, J=6.0, 5.7 Hz),6.85 (s, 1H), 7.20 (dd, 1H, J=6.9, 6.9 Hz), 7.40 (d, 1H, 7.8 Hz), 7.61(m, 2H), 7.80 (d, 1H J=8.0 Hz), 7.84 (d, H, J=8.9 Hz), 7.92 (dd, 1H,J=7.9, 7.9 Hz), 8.36 (d, 1H, J=4.9 Hz); MS (ESP+) 374.2 (M+1).

EXAMPLE 10N-(2-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-ethyl)-acetamide

In a sealed tube, a solution of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.192 mmol; see Example 2 for its preparation) andN-(2-amino-ethyl)-acetamide (0.689 mmol) in CH₃CN (2 mL) was warmed atreflux overnight. The reaction was concentrated in vacuo and purifiedvia preparatory HPLC (5→50% CH₃CN/H₂O) to yield 22 mg ofN-(2-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-ethyl)-acetamide.¹H NMR (d₆-DMSO, 400 MHz): 1.85 (s, 3H), 2.58 (s, 3H), 3.32(q, 2H,J=6.2), 3.46 (bm, 21H) 6.76 (bs, 1H), 7.31 (m, 1H), 7.50 (d, 1H, J=7.7Hz), 7.72 (dd, 1H, J=8.0 Hz), 7.81 (d, 1H, J=8.0 Hz), 7.90 (d, 1H, J=9.0Hz), 7.99 (d, 1H, J=8.0 Hz), 8.03 (dd, 1H, J=5.5 Hz), 8.33 (d, 1H, J=5.4Hz), 9.46 (s, 1H); MS (ESP+) 388.2 (M+1).

EXAMPLE 11N-(4-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butyl)-acetamide

In a sealed tube, a slurry of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.171 mmol; see Example 2 for its preparation), N-acetylputricinehydrochlorate (0.546 mmol) and Cs₂CO₃ (0.683 mmol in CH₃CN (2 mL) waswarmed at reflux overnight. The reaction was concentrated in vacuo andpurified via preparatory HPLC (5→50% CH₃CN/H₂O with 0.1% TFA) to yield12 mg ofN-(4-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butyl)-acetamideas the TFA salt. ¹H NMR (d-DMSO, 400 MHz): 1.51 (quintet, 2H, J=6.7 Hz),1.51 (quintet, 2H, J=6.7 Hz), 1.82 (s, 3H), 2.58 (s, 3H), 3.10 (q, 2H,6.5 Hz), 3.39 (bm, 2H), 6.75 (bs, 1H), 7.30 (bm, 1H), 7.49 (d, 1H J=7.1Hz), 7.71 (dd, 1H, J=7.7 Hz), 7.81 (d, 1H, J=8 Hz), 7.86 (m, 1H), 7.90(d, 1H, J=9 Hz), 7.99 (dd, 1H, J=8.0, 8.0 Hz), 8.30 (d, 1H, J=5.6 Hz);MS (ESP+) 416.2 (M+1).

EXAMPLE 12{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(2-pyridin-3-yl-ethyl)-amine

In a sealed tube, a solution of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.171 mmol; see Example 2 for its preparation) andpyridin-3-yl-ethylamine (0.565 mmol) in CH₃CN (2 mL) was warmed atreflux overnight. The reaction was concentrated in vacuo and purifiedvia preparatory HPLC (5→50% CH₃CN/H₂O with 0.1% TFA) to yield 40 mg of{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(2-pyridin-3-yl-ethyl)-amineas the TFA salt. ¹H NMR (d₆-DMSO, 400 MHz): 2.54 (s, 3H), 3.10 (t, 2H,J=6.5 Hz), 3.71 (m, 2H), 6.76 (bs, 1H), 7.23 (dd, 1H, J=6.8, 6.8 Hz),7.44 (d, 1H, J=7.8 Hz), 7.65 (dd, 1H, J=7.8 Hz), 7.72 (bm, 1H), 7.78 (d,1H, J=7.3 Hz), 7.83 (bm, 1H), 7.87 (d, 1H, 9.4 Hz), 7.95 (dd, 1H, J=8.3,8.3 Hz), 8.31 (d, 1H, J=5.7 Hz), 8.71 (d, 1H, J=6.2 Hz), 8.79 (bs, 1H);MS (ESP+) 408.2 (M+1).

EXAMPLE 1314-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(2-pyridin-4-yl-ethyl)-amine

In a sealed tube, a solution of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.171 mmol; see Example 2 for its preparation) andpyridin-4-yl-ethylamine (0.565 mmol) in CH₃CN (2 mL) was warmed atreflux overnight. The reaction was concentrated in vacuo and purifiedvia preparatory HPLC (5→50% CH₃CN/H₂O with 0.1% TFA) to yield 67 mg of{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(2-pyridin-4-yl-ethyl)-amineas the TFA salt. ¹H NMR (d₆-DMSO, 400 MHz): 2.53 (s, 3), 3.20 (t, 2H,J=6.9 Hz), 3.76 (q, 2H, J=6.4 Hz), 6.77 (bs, 1H), 7.21 (dd, 1H, J=7.0,7.0 Hz), 7.42 (d, 1H, 7.6 Hz), 7.63 (dd, 1H, J=8.2, 8.2 Hz), 7.68 (m,1H), 7.79 (d, 1H, J=7.7 Hz), 7.86 (d, 1H, J=9.0 Hz), 7.90 (m, 1H), 7.94(dd, 1H, J=7.8, 7.8 Hz), 8.32 (d, 1H, J=5.4 Hz), 8.79 (d, 1H, J=5.3 Hz);MS (ESP+) 408.2 (M+1).

EXAMPLE 14(4-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butyl)-carbamicacid tert-butyl ester

In a sealed tube, a solution of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.191 mmol; see Example 2 for its preparation) and(4-amino-butyl)-carbamic acid tert-butyl ester (0.611 mmol) in CH₃CN (2mL) was warmed at reflux overnight. The reaction was concentrated invacuo and purified via preparatory HPLC (5→50% CH₃CN/H₂O) to yield 44 mgof(4-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butyl)-carbamicacid tert-butyl ester. ¹H NMR (d₆-DMSO, 400 MHz): 1.39 (s, 9H), 1.50(quintet, 2H, J=6.8 Hz), 1.58 (quintet, 2H, J=6.8 Hz), 2.53 (s, 3 Hz),2.98 (q, 2H, J=6.6 Hz), 3.35 (m, 2H), 6.60 (bs, 1H), 6.81 (dd, 1H,J=5.3, 5.3 Hz), 7.09 (dd, 1H, J=6.4, 6.4 Hz), 7.28 (d, 1H, J=7.4 Hz),7.32 (m, 1H), 7.47 (ddd, 1H, J=1.1, 6.8, 6.8 Hz), 7.73 (dd, 1H, J=7.7,7.7 Hz), 7.81 (dd, 1H, J=7.7, 7.7 Hz), 8.19 (d, 1H, 5.5 Hz), 9.45 (bs,1H); MS (ESP+) 474.2 (M+1).

EXAMPLE 15N¹-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-butane-1,4-diamine

A solution of(4-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butyl)-carbamicacid tert-butyl ester (see Example 14 for its preparation) in 1:1CH₂Cl₂/TFA (2 mL) was allowed to stir for 30 min, then dried in vacuo toyield 12 mg ofN¹-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-butane-1,4-diamineas the tri-TFA salt. ¹H NMR (d-DMSO, 400 MHz): 1.67 (m, 4H), 2.56 (s,3H), 2.87 (m, 2H), 3.42 (m, 2H), 6.76 (bs, 1H), 7.28 (dd, 1×, J=6.9, 6.9Hz), 7.47 (d, 1H, J=7.9 Hz), 7.69 (m, 1H), 7.74 (bs, 2H), 7.81 (d, 1H,J=7.8 Hz), 7.90 (d, 1H, J=9.0 Hz), 7.97 (dd, 1H J=7.9, 7.9 Hz), 8.31 (d,1H, J=5.4 Hz), 9.49 (bs, 1H); MS (ESP+) 374.3 (M+1).

EXAMPLE 16(3-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-propyl)-carbamicacid tert-butyl ester

In a sealed tube, a solution of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.191 mmol; see Example 2 for its preparation) and(3-amino-propyl)-carbamic acid tert-butyl ester (0.602 mmol) in CH₃CN (2mL) was warmed at reflux overnight. The reaction was concentrated invacuo and purified via preparatory HPLC (5→50% CH₃CN/H₂O) to yield 27 mgof(3-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-propyl)-carbamicacid tert-butyl ester. ¹H NMR (d₆-DMSO, 400 MHz): 1.40 (s, 9H), 1.73(quintet, 2H, J=6.7 Hz), 2.53 (s, 3H), 3.05 (q, 2H, J=6.2 Hz), 3.36 (m,2H), 6.63 (bs, 1H), 6.87 (dd, 1H, J=5.6, 5.6 Hz), 7.12 (dd, 1H, 6.5, 6.5Hz), 7.30 (m, 1H), 7.31 (d, 1H, J=7.7 Hz), 7.51 (ddd, 1H, J=1.1, 6.8,6.8 Hz), 7.77 (dd, 2H, 7.7 Hz), 7.84 (dd, 1H, J=7.1, 7.1 Hz), 8.23 (d,1H, J=5.3 Hz), 9.47 (bs, 1H); MS (ESP+) 459.9 (M+1).

EXAMPLE 17N¹-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-propane-1,3-diamine

A solution of(3-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-propyl)-carbamicacid tert-butyl ester (see Example 16 for its preparation) in 1:1CH₂Cl₂/TFA (2 mL) was allowed to stir at RT for 30 min, then dried invacuo to yield 48 mg ofN′-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-propane-1,3-diamineas the tri-TFA salt. ¹H (d₆-DMSO, 400 MHz): 1.90 (quintet, 2H, J=7.8Hz), 2.55 (s, 3H), 2.93 (septet, 2H, J a 6.7 Hz), 3.45 (q, 2H, J=5.4Hz), 6.76 (bs, M1), 7.23 (dd, 1H, J=7.0, 7.0 Hz), 7.43 (d, 1H, J=7.4Hz), 7.67 (m, 41), 7.80 (d, 1H, J=7.9 Hz), 7.86 (d, 111 J=9.1 Hz), 7.95(dd, 1H, J=7.9, 7.9 Hz), 8.32 (d, 1H, J=5.3 Hz), 9.44 (bs, 1H); MS(ESP+) 360.2 (M+1).

EXAMPLE 18{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(3-morpholin-4-yl-propyl)-amine

In a sealed tube, a solution of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.205 mmol; see Example 2 for its preparation) and 3-propylaminomorpholine (0.670 mmol) in CH₃CN (2 mL) was warmed at reflux overnight.The reaction was concentrated in vacuo and purified via preparatory HPLC(5→50% CH₃CN/H₂O with 0.1% TFA) to yield 20 mg of{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(3-morpholin-4-yl-propyl)-amineas the TFA salt. ¹H NMR (d₆-DMSO, 400 MHz): 1.97 (m, 2H), 2.51 (s, 3H),3.08 (m, 2H), 3.18 (m, 2H), 3.41 (m, 4H), 3.64 (bs, 2H), 3.94 (bs, 2H),6.73 (bs, 1H), 7.17 (dd, 1H, J=6.5, 6.5 Hz), 7.37 (d, 1H, J=7.8 Hz),7.58 (m, 1H), 7.61 (m, 1H), 7.76 (d, 1H, J=8.0 Hz), 7.81 (d, 1H, J=9.0Hz), 7.89 (dd, 1H, J=7.6, 7.6 Hz), 8.28 (d, 1H, J=5.4 Hz), 9.39 (bs,1H); MS (ESP+) 430.2 (M+1).

EXAMPLE 19{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(2-pyridin-2-yl-ethyl)-amine

In a sealed tube, a solution of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.193 mmol; see Example 2 for its preparation) and2-pyridin-2-yl-ethylamine (0.641 mmol) in CH₃CN (2 mL) was warmed atreflux overnight. The reaction concentrated in vacuo and purified viapreparatory HPLC (5→50% CH₃CN/H₂O) to yield 24 mg of{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl)-(2-pyridin-2-yl-ethyl)-amine.¹H NMR (CDCl₃, 400 MHz): 2.43 (s, 3H), 3.06 (t, 2H, J=6.7 Hz), 3.71 (q,2H, J=6 Hz), 6.63 (d, 1H, J=5.0 Hz), 7.07 (ddd, 1H, J=0.8, 7.1, 7.1 Hz),7.23 (m, 1H), 7.28 (m, 2H), 7.48 (m, 1H), 7.72 (m, 21), 7.81 (t, 1H, 7.9Hz), 8.20 (d, 1H, J=5.4 Hz), 8.53 (dddd, 1H, J=0.8, 5.0, 5.0, 5.0 Hz),9.47 (d, 1, J=7.1 Hz); MS (ESP+) 408.1 (M+1).

EXAMPLE 204-(2-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-ethyl)-benzenesulfonamide

In a sealed tube, a solution of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.193 mmol; see Example 2 for its preparation) and4-(2-amino-ethyl)-benzenesulfonamide (0.639 mmol) in DMF (2 mL) waswarmed at reflux overnight. The reaction was concentrated in vacuo andpurified via preparatory HPLC (5→50% CH₃CN/H₂O) to yield 13 mg of4-(2-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-ethyl)-benzenesulfonamide.¹H NMR (d₆-DMSO, 400 MHz): 2.43 (s, 3H), 2.98 (t, 2H, J=6.5 Hz), 3.59(q, 2H, J=6.5 Hz), 6.66 (bs, 1H), 7.07 (dd, 1H, J=7.0, 7.0 Hz), 7.25 (m,3H), 7.48 (m, 4H), 7.75 (m, 4H), 7.81 (dd, 1H, J=7.7, 7.7 Hz), 8.23 (d,1H, J=5.0 Hz), 9.40 (bs, 1H); MS (ESP+) 486.0 (M+1).

EXAMPLE 21Methyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine

In a sealed tube, a solution of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.137 mmol; see Example 2 for its preparation) and 2.00 Mmethylamine/THF (1.00 mmol) in CH₃CN (2 mL) was warmed at refluxovernight. The reaction was concentrated in vacuo and purified viapreparatory HPLC (5→50% CH₃CN/) to yield 17 mg ofmethyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine.¹H NMR (d₆-DMSO, 400 MHz): 2.46 (s, 3H), 2.93 (d, 3H, J=5.0 Hz), 6.66(d, 1H, J=5.4 Hz), 7.12 (dd, 1H J=6.7, 6.7 Hz), 7.28 (m, 1H), 7.32 (d,1H, J=7.8 Hz), 7.51 (m, 1H), 7.78 (m, 2H), 7.85 (dd, 1H, J=7.6, 7.6 Hz),8.25 (d, 1H, J=5.0 Hz), 9.49 (d, 1H, J=7.0 Hz); MS (ESP+) 317.2 (M+1).

EXAMPLE 22Dimethyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine

In a sealed tube, a solution of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.136 mmol; see Example 2 for its preparation) and 2.0 Mdimethylamine/THF (1 mmol) in CH₃CN (2 mL) was warmed at refluxovernight. The reaction was concentrated in vacuo and purified viapreparatory HPLC (5→50% CH₃CN/H₂O) to yield 17 mg ofdimethyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine.¹H NMR (d₆-DMSO, 400 MHz): 2.46 (s, 3H), 3.24 (s, 6H), 6.70 (d, 1H,J=5.0 Hz), 7.14 (dd, 1H, J=6.8, 6.8 Hz), 7.32 (d, 1H, J=7.3 Hz), 7.52(dd, 1H, J=8.0, 8.0 Hz), 7.79 (m, 2H), 7.85 (d, 1H, J=7.8, 7.8 Hz), 8.33(d, 1H, J=5.4, 5.4 Hz), 9.39 (d, 1H, J=7.2 Hz); MS (ESP+) 331.2 (M+1).

EXAMPLE 23(3-Imidazol-1-yl-propyl)-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine

In a sealed tube, a solution3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.273 mmol; see Example 2 for its preparation) andimidazol-1-yl-propylamine (0.905 mmol) in CH₃CN (4 mL) was warmed atreflux overnight. The reaction was concentrated in vacuo and purifiedvia preparatory HPLC (5→50% CH₃CN/H₂O with 0.1% TFA) to yield 8 mg of(3-imidazol-1-yl-propyl)-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amineas the TFA salt. ¹H NMR (d₆-DMSO, 400 MHz): 2.12 (p, 2H, J=6.8 Hz), 2.45(s, 3H), 3.37 (m, 2H), 4.23 (t, 2H, J=7.1 Hz), 6.70 (bs, 1H), 7.11 (dd,1H, J=6.9, 6.9 Hz), 7.31 (d, 1H, J=7.6), 7.34 (bs, 1H), 7.50 (m, 2H),7.57 (bs, 1H), 7.78 (m, 2H), 7.85 (dd, 1H, J=8.0, 8.0 Hz), 8.26 (d, 1H,5.3 Hz), 8.46 (bs, 1H), 9.38 (bs, 1H); MS (ESP+) 411.2 (M+1).

EXAMPLE 243-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-phenol

In a sealed tube, a slurry of solid KIDS (0.501 mmol) and 3-aminophenol(0.458 mmol) in anhydrous dioxane (2 mL) was stirred for 1 hour.3-(2-Methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.137 mmol; see Example 2 for its preparation) was added to thereaction and the mixture was allowed to stir for 2 days at 80° C. Themixture was concentrated in vacuo and purified via preparatory HPLC(5→50% CH₃CN/H₂O with 0.1% TFA) to yield 12 mg of3-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-phenolas the TFA salt. ¹H NMR (d₆-DMSO, 400 MHz): 2.55 (s, 3H), 6.70 (m, 2H),7.02 (dd, 1H, J=7.1, 7.1 Hz Hz), 7.28 (m, 1H), 7.40 (d, 1H, J=5.3 Hz),7.44 (d, 1H, J=7.3 Hz), 7.58 (dd, 1H, J=7.6, 7.6 Hz), 7.83 (m, 2H), 7.95(dd, 1H, J=7.3, 7.3 Hz), 8.62 (d, 1H, J=5.0 Hz), 9.13 (d, 1H, J=6.5 Hz);MS (ESP+) 395.2 (M+1).

EXAMPLE 25{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-[1,3,4]thiadiazol-2-yl-amine

In a sealed tube, a slurry of solid KHMDS (0.501 mmol) and[1,3,4]thiadiazol-2-ylamine (0.454 mmol) in anhydrous dioxane (2 mL) wasstirred for 1 hour.3-(2-Methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.137 mmol; see Example 2 for its preparation) was added to thereaction and the mixture was allowed to stir for 2 days at 80° C. Themixture was concentrated in vacuo and purified via preparatory HPLC(5→50% CH₃CN/H₂O with 0.1% TFA) to yield 23 mg of{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-[1,3,4]thiadiazol-2-yl-amineas the TFA salt. ¹H NMR (d₆-DMSO, 400 MHz): 2.51 (s, 3H), 7.17 (m, 2H),7.37 (d, 1H, 7.4 Hz), 7.60 (dd, 1H, J=7.5, 7.5 Hz), 7.86 (m, 3H), 8.61(d, 1H, J=5.3 Hz), 9.07 (s, 1H), 9.59 (bs, 1H); MS (ESP+) 387.1 (M+1).

EXAMPLE 26(5-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-pentyl)-carbamicacid tert-butyl ester

In a sealed tube, a solution of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.205 mmol; see Example 2 for its preparation) and(5-amino-pentyl)-carbamic acid tert-butyl ester (0.677 mmol) inacetonitrile (2 mL) was warmed at reflux overnight. The reaction wasconcentrated in vacuo and purified via preparatory HPLC (5→50% CH₃CN/H₂Owith 0.1% TFA) to yield 65 mg of(5-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-pentyl)-carbamicacid tert-butyl ester as the TFA salt. ¹H NMR (d₆-DMSO, 400 MHz): 1.36(s, 9H), 1.40 (m, 2H), 1.62 (m, 2H), 2.58 (s, 3H), 2.96 (m, 2H), 3.37(m, 2H), 6.78 (bs, 1H), 6.82 (bs, 1H), 7.30 (dd, 1H, J=5.0, 5.0 Hz),7.49 (d, 1H, J=7.5 Hz), 7.70 (dd, 1H, J=8.1, 8.1 Hz), 7.81 (d, 1H, J=7.5Hz), 7.90 (d, 1H, J=8.1 Hz), 7.95 (dd, 1H, J=7.5, 7.5 Hz), 8.30 (d, 1H,J=5.0 Hz); MS (ESP+) 488.2 (M+1).

EXAMPLE 27[3-(4-Methyl-piperazin-1-yl)-propyl]-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine

In a sealed tube, a solution of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.205 mmol; see Example 2 for its preparation) and3-(4-methyl-piperazin-1-yl)-propylamine (0.680 mmol) in acetonitrile (2mL) was warmed to reflux overnight. The mixture was concentrated itvacuo and purified on the preparatory HPLC (5→50% CH₃CN/H₂O) to yield 20mg of[3-(4-methyl-piperazin-1-yl)-propyl]-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine.¹H NMR (d₆-DMSO, 400 MHz): 1.78 (m, 2H), 2.28 (s, 3H), 2.46 (s, 3H),3.38 (m, 2H), 6.65 (bs, 1H), 7.11 (ddd, 1H, J=1.0, 7.0, 7.0 Hz), 7.32(d, 1H, J=7.3 Hz), 7.40 (s, 1H), 7.51 (m, 1H, J=7.8 Hz), 7.78 (m, 2H),7.85 (dd, 1H, J=7.8, 7.8 Hz), 8.24 (d, 1H, J=5.5 Hz), 9.45 (bs, 1H); MS(ESP+) 443.4 (M+1).

EXAMPLE 28Cyclopropyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine

In a sealed tube, a solution of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.205 mmol; see Example 2 for its preparation) and cyclopropylamine(14.4 mmol) in acetonitrile (2 mL) was warmed to reflux overnight. Themixture was concentrated in vacuo and purified via preparatory HPLC(5→50% CH₃CN/H₂O with 0.1% TFA) to yield 40 mg ofcyclopropyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amineas the TFA salt. ¹H NMR (d₆-DMSO, 400 MHz): 0.66 (m, 2H), 0.84 (m, 2H),2.58 (s, 3H), 2.82 (m, 1H), 6.82 (d, 2H, J=5.5 Hz), 7.30 (dd, 1H, J=7.5,7.5 Hz), 7.48 (d, 1H, J=7.9 Hz), 7.70 (dd, 1H, J=8.1, 8.1 Hz), 7.83 (d,1H, J=7.5 Hz), 7.89 (d, 1H, 9.3 Hz), 7.98 (dd, 1H, J=8.0, 8.0 Hz), 8.30(d, 1H, J=5.6 Hz), 9.74 (bs, 1H); MS (ESP+) 343.3 (M+1).

EXAMPLE 292-(6-Methyl-pyridin-2-yl)-3-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine

In a sealed tube, a solution of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.205 mmol; see Example 2 for its preparation) and pyrrolidine (1.20mmol) in acetonitrile (2 mL) was warmed to reflux overnight. The mixturewas concentrated in vacuo and purified via preparatory HPLC (5→80%CH₃CN/H₂O with 0.1% TFA) to yield 40 mg2-(6-methyl-pyridin-2-yl)-3-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-imidazo[1,2-a]pyridineas the TFA salt. ¹H NMR (d₆-DMSO, 400 MHz): 2.00 (bm, 4H), 2.54 (s, 3H),3.60 (bm, 4H), 6.71 (bs, 1H), 7.26 (m, 1H), 7.44 (d, 1H, 7.3 Hz), 7.68(bm, 1H), 7.77 (d, 1H, J=7.9 Hz), 7.86 (d, 1H, J=8.9 Hz), 7.95 (bm, 1H),8.33 (d, 1H, J=5.4 Hz), 9.46 (d, 1H, J=6.1 Hz); MS (ESP+) 357.4 (N+1).

EXAMPLE 302-(6-Methyl-pyridin-2-yl)-3-(2-piperidin-1-yl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine

In a sealed tube, a solution of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.205 mmol; see Example 2 for its preparation) and piperidine (1.01mmol) in acetonitrile (2 mL) was warmed to reflux overnight. The mixturewas concentrated in vacuo and purified via preparatory HPLC (5→80%CH₃CN/H₂O with 0.1% TFA) to yield 24 mg of2-(6-methyl-pyridin-2-yl)-3-(2-piperidin-1-yl-pyrimidin-4-yl)-imidazo[1,2-a]pyridineas the TFA salt. ¹H NMR (d₆-DMSO, 400 MHz): 1.59 (m, 4H), 1.67 (m, 2H),2.55 (s, 3H), 3.81 (m, 4H), 6.74 (d, 1H, J=5.0 Hz), 7.24 (ddd, 1H,J=0.8, 7.7, 7.7 Hz), 7.43 (d, 1H, 7.6 Hz), 7.63 (m, 1H), 7.77 (d, 1H,J=7.7 Hz), 7.84 (d, 1H, J=9.2 Hz), 7.92 (t, 1H, J=7.9 Hz), 8.37 (d, 1H,J=5.2 Hz), 9.18 (d, 1H, J=7.1 Hz); MS (ESP+) 371.4 (M+1).

EXAMPLE 31(2-Methoxy-ethyl)-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine

In a sealed tube, a solution of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.205 mmol; see Example 2 for its preparation) and 2-methoxy-ethylamine(1.16 mmol) in acetonitrile (2 mL) was warmed to reflux overnight. Themixture was concentrated in vacuo and purified via preparatory HPLC(5→80% CH₃CN/H₂O with 0.1% TFA) to yield 42 mgof(2-methoxy-ethyl)-4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amineas the TFA salt. ¹H NMR (d-DMSO, 400 MHz): 2.58 (s, 3H), 3.34 (s, 3H),3.57 (bm, 4H), 6.77 (bs, 1H), 7.28 (dd, 1H, J=7.1, 7.1 Hz), 7.49 (d, 1H,J=8 Hz), 7.78 (dd, 1H, J=8.7, 8.7 Hz), 7.82 (d, 1H J=7.7 Hz), 7.89 (d,1H, J=9.3 Hz), 7.99 (dd, 1H, J=7.8, 7.8 Hz), 8.31 (d, 1H, J=5.5 Hz),9.50 (bs, 1H); MS (ESP+) 361.4 (M+1).

EXAMPLE 323-[2-(4-Methyl-piperazin-1-yl)-pyrimidin-4-yl]-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine

In a sealed tube, a solution of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.205 mmol; see Example 2 for its preparation) and 1-methyl-piperazine(0.900 mmol) in acetonitrile (2 mL) was warmed to reflux ovenight. Themixture was concentrated in vacuo and purified via preparatory HPLC(5→80% CH₃CN/H₂O with 0.1% TFA) to yield 19 mg of3-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridineas the TFA salt. ¹H NMR (4-DMSO, 400 MHz): 2.45 (s, 3H), 2.89 (s, 3H),3.13 (m, 2H), 3.33 (m, 2H), 3.57 (m, 2H), 4.74 (m, 2H), 6.94 (d, 1H,J=5.1 Hz), 7.15 (dd, 1H, J=7.0, 7.0 Hz), 7.35 (d, 1H, J=7.9 Hz), 7.57(dd, 1H, J=7.7, 7.7 Hz), 7.80 (d, 1H, J=8.2 Hz), 7.85 (d, 1H, J=9.6 Hz),7.89 (dd, 1H, J=7.9, 7.9 Hz), 8.46 (d, 1H, J=5.5 Hz), 9.16 (d, 1H, J=7.0Hz), 9.93 (bs, 1H); MS (ESP+) 386.4 (M+1).

EXAMPLE 333-[2-(2-Methyl-aziridin-1-yl)-pyrimidin-4-yl]-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine

In a sealed tube, a solution of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.137 mmol; see Example 2 for its preparation) and 2-methyl-aziridine(0.849 mmol) in acetonitrile (2 mL) was warmed to reflux overnight. Themixture was concentrated in vacuo and purified via preparatory HPLC(5→50% CH₃CN/H₂O with 0.1% TFA) to yield 11 mg of3-[2-(2-methyl-aziridin-1-yl)-pyrimidin-4-yl]-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridineas the TFA salt. ¹H NMR (d₆-DMSO, 400 MHz): 1.16 (d, 3H, J=5.8 Hz), 2.56(s, 3H), 3.36 (m, 2H), 3.90 (m, 1H), 6.75 (m, 1H), 7.16 (m, 1H), 7.45(m, 1H), 7.72 (m, 2H), 7.91 (m, 1H), 8.20 (m, 1H), 9.54 (m, 1H); MS(ESP+) 343.2 (M+1).

EXAMPLE 34{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(2H-pyrazol-3-yl)-amine

In a sealed tube, a slurry of solid KHMDS (0.501 mmol) and2H-pyrazol-3-ylamine (0.454 mmol) in anhydrous dioxane (2 mL) wasstirred for 1 hour.3-(2-Methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.137 mmol; see Example 2 for its preparation) was added to thereaction and the mixture was allowed to stir for 2 days at 80° C. Themixture was passed through a silica plug, concentrated in vacuo andpurified via preparatory HPLC (5→80% CH₃CN/H₂O with 0.1% TFA) to yield21 mg of{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(2H-pyrazol-3-yl)-amineas the TFA salt. ¹H NMR (d₆-DMSO, 400 MHz): 2.47 (s, 3H), 5.94 (d, 1H,J=2.7 Hz), 7.22 (dd, 1H, J=7.0, 7.0 Hz), 7.39 (m, 1H), 7.61 (dd, 1H,J=8.4, 8.4 Hz), 7.90 (m, 3H), 8.36 (d, 1H, J=2.2 Hz), 8.64 (d, 1H, J=4.9Hz), 9.56 (d, 1H, J=7.5 Hz); MS (ESP+) 369.2 (M+1).

EXAMPLE 352-(6-Methyl-pyridin-2-yl)-3-[2-(1H-tetrazol-5-yl)-pyrimidin-4-yl]-imidazo[1,2-a]pyridine

A solution of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.200 mmol; see Ex. 2 for its preparation) and sodium cyanide (0.671mol) in anhydrous DMF (2 mL) was warmed to 100° C. in a sealed tube for4.5 h. After cooling to RT, the solution was filtered through a Celitepad and concentrated in vacuo to give a dark solid. The solid wasslurried in DMSO/water, cooled to 0° C., filtered, washed with coldwater and air dried to give 0.0274 g of a tan solid identified as4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidine-2-carbonitrile.MS (ESP+) 313.20 (M+1).

In a sealed tube,4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidine-2-carbonitrile(0.240 mmol), NaN₃ (1.72 mmol), and NH₄Cl (1.27 mmol) were addedsequentially to DMF (3 mL). The mixture was heated to 110° C. over twodays. The reaction was concentrated in vacuo and purified viapreparatory HPLC (CH₃CN/H₂O gradient) to yield 50 mg of2-(6-methyl-pyridin-2-yl)-3-[2-(1H-tetrazol-5-yl)-pyrimidin-4-yl]-imidazo[1,2-a]pyridine.¹H NMR (CDCl₃, 400 MHz): 2.48 (s, 3H), 7.22 (dt, 1H, J=1.1, 6.6 Hz),7.33 (m, 2H), 7.57 (m, 2H), 7.84 (d, 1H, J=8.7 Hz), 7.91 (m, 2H), 8.78(d, 1H, J=5.6 Hz), 9.87 (d, 1H, J=7.4 Hz); MS (ESP−) 354.1 (M−1).

EXAMPLE 363-(2-Azetidin-1-yl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine

In a sealed tube, a solution of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.147 mmol; see Example 2 for its preparation) and azeridine (0.297mmol) in CH₃CN (2 mL) was allowed to stir at reflux overnight. Thereaction was concentrated in vacuo and purified via preparatory HPLC(5→90% CH₃CN/H₂O with 0.1% TFA) to yield 18 mg of3-(2-azetidin-1-yl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridineas the TFA salt. ¹H NMR (d₆-DMSO, 400 MHz): 2.43 (quint, 2H, J=7.2 Hz),2.54 (s, 1H), 4.20 (t, 4H, J=7.5 Hz), 6.81 (d, 1H, J=5.3 Hz), 7.25 (dd,2H, J=6.9, 6.9 Hz), 7.44 (d, 1H, J=7.9 Hz), 7.65 (dd, 1H, J=7.4, 8.4Hz), 7.80 (d, 1H, J=7.7 Hz), 7.86 (d, 1H, J=9.0 Hz), 7.95 (dd, 1H,J=7.7, 7.9 Hz), 8.35 (d, 1H, J=5.2 Hz), 9.41 (d, 1H, J=8.9 Hz); MS(ESP+) 343.2 (M+1).

EXAMPLE 37Cyclopentyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine

In a sealed tube, a solution of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.137 mmol; see Example 2 for its preparation) and cyclopentylamine(0.452 mmol) in CH₃CN (2 mL) was allowed to stir at reflux overnight.The reaction was concentrated in vacuo and purified via preparatory HPLC(5→50% CH₃CN/H₂O with 0.1% TFA) to yield 11 mg ofcyclopentyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amineas the TFA salt. ¹H NMR (d₆-DMSO, 400 MHz): 1.62 (m, 4H), 1.71 (m, 2H),1.95 (m, 2H), 2.54 (s, 3H), 4.19 (m, 2H), 6.71 (d, 1H, J=4.8 Hz), 7.26(dd, 1H, J=7.1, 7.1 Hz), 7.44 (d, 1H, J=7.4 Hz), 7.65 (m, 1H), 7.77 (d,1H, J=7.8 Hz), 7.86 (d, 1H, J=9.0 Hz), 7.94 (dd, 1H, J=7.9, 7.9 Hz),8.25 (d, 1H, J=5.4 Hz), 9.50 (bs, 1H); MS (ESP+) 371.1 (M+1).

EXAMPLE 38{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-((S)-1-phenyl-ethyl)-amine

In a sealed tube, a solution of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.137 mmol; see Example 2 for its preparation) and(S)-benzylmethylamine (1.37 mmol) in CH₃CN (2 mL) was allowed to stir atreflux overnight. The reaction was concentrated in vacuo and purifiedvia preparatory HPLC (5→50% CH₃CN/H₂O with 0.1% TFA) to yield 11 mg of{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-((S)-1-phenyl-ethyl)-amineas the TFA salt. ¹H NMR (d₆-DMSO, 400 MHz): 1.54 (d, 3H, J=7.0 Hz), 2.56(s, 3H), 5.09 (bs, 1H), 6.68 (d, 1H, J=5.2 Hz), 7.31 (m, 1H), 7.44 (m,6H), 7.65 (m, 1H), 7.77 (d, 1H, J=7.3 Hz), 7.85 (d, 1H, J=7.3 Hz), 7.96(dd, 1H, J=8.3, 7.3 Hz), 8.23 (m, 1H), 8.30 (d, 1H, J=5.0 Hz); MS (ESP+)407.2 (M+1).

EXAMPLE 39{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-((R)-1-phenyl-ethyl)-amine

In a sealed tube, a solution of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.137 mmol; see Example 2 for its preparation) and(R)-benzylmethylamine (1.37 mmol) in CH₃CN (2 mL) allowed to stir atreflux overnight. The reaction was concentrated in vacuo and purifiedvia preparatory HPLC (5→50% CH₃CN/H₂O with 0.1% TFA) to yield 11 mg of{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-((S)-1-phenyl-ethyl)-amineas the TFA salt. ¹H NMR (d₆-DMSO, 400 MHz): 1.54 (d, 3H, J=7.0 Hz), 2.56(s, 3H), 5.09 (bs, 1H), 6.68 (d, 1H, J=5.2 Hz), 7.31 (m, 1H), 7.44 (m,6H), 7.65 (m, 1H), 7.77 (d, 1H, J=7.3 Hz), 7.85 (d, 1H, J=7.3 Hz), 7.96(dd, 1H, J=8.3, 7.3 Hz), 8.23 (m, 1H), 8.30 (d, 1H, J=5.0 Hz); MS (ESP+)407.2 (M+1).

EXAMPLE 408-Methyl-2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine

Hydrogen bromide/acetic acid (30 wt %, 7.70 mmol) and 1.0 Mbromine/acetic acid (2.0 mmol) was added to a solution of1-(6-methyl-pyridin-2-yl)-2-(2-methylsulfanyl-pyrimidin-4-yl)-ethanone(1.54 mmol; see Example 1(b) for its preparation) and catalytic BHT inglacial acetic acid (10 mL) at RT with formation of a precipitate. After1 h the reaction was diluted with ether (40 mL), stirred for 30 minutes,the precipitate was then filtered and washed with Et₂O (Extreme cautionwas taken to make sure the precipitate did not dry completely). Theprecipitate was slurried in CH₃CN (10 mL), added to a slurry of Hunig'sbase (4.58 mmol) and 3-methyl-2-aminopyridine (1.85 mmol) at RT and thenwarmed overnight at 55° C. A precipitate formed upon cooling to RT. Theslurry was diluted with water (10 mL), filtered, washed with cold CH₃CNto give 211 mg of a tan solid identified as8-methyl-2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine.

EXAMPLE 413-(2-methanesulfonyl-pyrimidin-4-yl)-8-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine

4.0N Sulfuric acid (0.06 mmol), catalytic sodium tungstate dihydrate,and 30 wt % hydrogen peroxide (1.96 mmol) was added to a slurry of8-methyl-2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine(0.608 mmol; see Ex. 40 for its preparation) in methanol (4 mL) at 50°C. After 3.5 h the reaction was diluted with water (10 mL) and warmed at50° C. for a further 0.5 h. The reaction was then cooled to RT, quenchedwith saturated sodium thiosulfate, the pH adjusted to 6 with 1M NaOH andfiltered to give 0.200 g of a tan solid identified as3-(2-methanesulfonyl-pyrimidin-4-yl)-8-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine.¹H NMR (d₆-DMSO, 400 MHz): 2.44 (s, 3H), 2.66 (s, 3H), 3.53 (s, 3H),7.15 (dd, 1H, J=7.0, 7.0 Hz), 7.36 (d, 1H, J=7.7 Hz), 7.44 (d, 1H, J=6.6Hz), 7.97 (m, 31), 8.05 (d, 1H, J=5.3 Hz), 8.99 (d, 1H, J=5.1 Hz), 9.24(d, 1H, J=7.0 Hz); MS (ESP+) 380.2 (M+1).

EXAMPLE 424-[8-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine

In a sealed tube, a slurry of3-(2-methanesulfonyl-pyrimidin-4-yl)-8-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.263 mmol; prepared in accordance with Ex. 2) and NH₄OAc (6.60 mmol)in 2:1 dioxane/water (3 mL) was warmed at 100° C. for 7 days. Thereaction was cooled to RT, diluted with EtOAc (25 ml), washed with H₂O,brine, dried (Na₂SO₄), concentrated in vacuo and purified viapreparatory HPLC (CH₃CN/H₂O gradient with 0.1% TFA) to give 30 mg of asolid identified as the TFA salt of4-[8-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine.¹H NMR (d₆-DMSO, 400 MHz): 2.65 (s, 3H), 6.75 (d, 1H, J=5.8 Hz), 7.17(dd, 1H, J=7.1, 7.1 Hz), 7.46 (d, 1H, J=8.1 Hz) 7.50 (d, 1H, J=6.5 Hz),7.83 (d, 1H, J=7.7 Hz), 7.97 (dd, 1H, J=7.6, 7.6 Hz), 8.20 (d, 1H, J=6.0Hz), 9.57 (d, 1H, J=7.3 Hz); MS (ESP+) 317.2 (M+1).

EXAMPLE 434-[7-Methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine

Hydrogen bromide/acetic acid (30 wt %, 7.70 mmol) and 1.0 Mbromine/acetic acid (2.0 mmol) was added to a solution of1-(6-methyl-pyridin-2-yl)-2-(2-methylsulfanyl-pyrimidin-4-yl)-ethanone(1.54 mmol; see Example 1(b) for its preparation) and catalytic BHT inglacial acetic acid (10 mL) at RT with formation of a precipitate. After1 h the reaction was diluted with ether (40 mL), stirred for 30 minutes,the precipitate was then filtered and washed with Et₂O (extreme cautionwas taken to make sure the precipitate did not dry completely). Theprecipitate was slurried in CH₃CN, added to a mixture of Hunig's baseand 4-methyl-2-aminopyridine (1.86 mmol) at RT and then warmed overnightat 55° C. A precipitate formed upon cooling to RT. The slurry wasdiluted with water (10 mL), filtered, washed with cold CH₃CN to give 211mg of a solid identified as7-methyl-2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine.¹H NMR (CDCl₃, 300 MHz): 2.49 (s, 3H), 2.56 (s, 3H), 2.64 (s, 3H), 6.84(m, 1H), 7.20 (m, 2H), 7.58 (m, 1H), 7.73 (m, 2H), 8.35 (d, 1H J=5.4Hz), 9.41 (d, 1H, J=6.9 Hz); MS (ESP+) 373.3 (M+1).

EXAMPLE 443-(2-methanesulfonyl-pyrimidin-4-yl)-7-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine

4.0N Sulfuric acid (0.02 mmol), catalytic sodium tungstate dihydrate,and 30 wt % hydrogen peroxide (X mmol) was added to a slurry7-methyl-2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine(0.274 mmol; prepared in accordance with Ex. 1) in methanol (3 mL) at55° C. After 3.5 h the reaction was diluted with water (10 mL) andwarmed at 55° C. for a further 0.5 h. The reaction was then cooled toRT, quenched with saturated sodium thiosulfate, the pH adjusted to 6with 1M NaOH and filtered to give 0.070 g of a yellow solid identified3-(2-methanesulfonyl-pyrimidin-4-yl)-7-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine.¹H NMR (d₆-DMSO, 400 MHz): 2.42 (s, 3H), 2.46 (s, 3H), 3.49 (s, 3H),7.11 (dd, 1H, J=1.6, 7.2 Hz), 7.36 (d, 1H, J=7.0 Hz), 7.67 (bs, 1H),7.92 (m, 2H), 8.08 (d, 1H J=5.5 Hz), 8.98 (d, 1H, J=5.5 Hz); MS (ESP+)380.2 (M+1).

EXAMPLE 454-[7-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine

In a sealed tube, a slurry of3-(2-methanesulfonyl-pyrimidin-4-yl)-7-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.184 mmol; see Example 44 for its preparation) and NH₄OAc (4.60 mmol)in 2:1 dioxane/water (3 mL) was warmed to 100° C. for 7 days. Thereaction was cooled to RT, diluted with EtOAc (25 ml), washed with H₂O,brine, dried (Na₂SO₄), concentrated in vacuo and purified viapreparatory HPLC (CH₃CN/H₂O gradient with 0.1% TFA) to yield 22 mg of asolid identified as the TFA salt of4-[7-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine.¹H NMR (d₆-DMSO, 400 MHz): 2.53 (s, 3H), 2.57 (s, 3H), 6.80 (d, 1H,J=6.0 Hz), 7.19 (d, 1H, J=7.9 Hz), 7.47 (d, 1H, J=7.6 Hz), 7.71 (bs,1H), 7.78 (d, 1H, J=7.8 Hz), 7.96 (dd, 1H, J=7.6, 7.6 Hz), 8.23 (d, 1H,J=6.2 Hz), 9.56 (d, 1H, J=6.4 Hz); MS (ESP+) 317.3 (M+1).

EXAMPLE 466-Chloro-2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine

Hydrogen bromide/acetic acid (30 wt %, 7.70 mmol) and 1.0 Mbromine/acetic acid (2.0 mmol) was added to a solution of1-(6-methyl-pyridin-2-yl)-2-(2-methylsulfanyl-pyrimidin-4-yl)-ethanone(1.54 mmol; see Example 1(b) for its preparation) and catalytic BHT inglacial acetic acid (10 mL) at RT with formation of a precipitate. After1 h the reaction was diluted with ether (40 mL), stirred for 30 minutes,the precipitate was then filtered and washed with Et₂O (Extreme cautionwas taken to make sure the precipitate did not dry completely). Theprecipitate was slurried in CH₃CN (10 mL). 4-Chloro-2-aminopyridine(1.85 mmol) and Hunig's base (4.58 mmol) was added to this slurry andthe mixture was allowed to stir overnight at 55 C under a nitrogenatmosphere. A precipitate formed upon cooling to RT. The slurry wasdiluted with water (10 mL), filtered and washed with cold CH₃CN to give124 mg of a impure tan solid identified as6-chloro-2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine.MS (ESP+) 368.0 (M+1).

EXAMPLE 476-Chloro-3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine

4.0N Sulfuric acid (0.02 mmol), catalytic sodium tungstate dihydrate,and 30 wt % hydrogen peroxide (0.98 mmol) was added to a slurry6-chloro-2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine(0.274 mmol; see Ex. 46 for its preparation) in methanol (2 mL) at 55°C. After 3.5 h the reaction was diluted with water (10 mL) and warmed at55° C. for a further 0.5 h. The reaction was then cooled to RT, quenchedwith saturated sodium thiosulfate, the pH adjusted to 6 with 1M NaOH andfiltered to give 0.050 g of a yellow solid identified as impure6-chloro-3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine.MS (ESP+) 400.0 (M+1).

EXAMPLE 484-[6-Chloro-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine

In a sealed tube, a slurry of6-chloro-3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(0.125 mmol; see Example 47 for its preparation) and NH₄OAc (6.60 mmol)in 1:1 dioxane/water (2 mL) was warmed at 100° C. for 5 days. Thereaction cooled to RT, diluted with EtOAc (25 ml), washed with H₂O,brine, dried (Na₂SO₄), concentrated in vacuo and purified viapreparatory HPLC (CH₃CN/H₂O gradient with 0.1% TFA) to yield 4 mg of asolid identified as the TFA salt of4-[6-chloro-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine.¹H NM (d₆-DMSO, 400 MHz): 2.50 (s, 3H), 6.84 (d, 1H, J=6.0 Hz), 7.45 (d,1H, J=8.5 Hz), 7.72 (d, 1H, J=10.1 Hz), 7.86 (d, 1H, J=6.9 Hz), 7.96 (m,2H), 8.25 (d, 1H, J=6.0 Hz), 9.72 (s, 1H); MS (ESP+) 337.1 (M+1).

EXAMPLE 49[2-(6-Methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridin-6-yl]-methanol

Hydrogen bromide/acetic acid (30 wt %, 7.70 mmol) and 1.0 Mbromine/acetic acid (2.0 mmol) was added to a solution of1-(6-methyl-pyridin-2-yl)-2-(2-methylsulfanyl-pyrimidin-4-yl)-ethanone(1.54 mmol; see Example 1(b) for its preparation) and catalytic BHT inglacial acetic acid (10 mL) at −15° C. with formation of a precipitate.After 0.25 h the reaction was diluted with ether (40 mL), stirred for 5minutes, the precipitate was then filtered and washed with Et₂O under anitrogen flow (Extreme caution was taken to make sure the precipitatedid not dry completely). The precipitate was added to a flask containing(6-amino-pyridin-3-yl)-methanol (2.06 mmol) under a nitrogen atmosphere,slurried in toluene (8 mL) and warmed to 100° C. Diisopropylethylamine(11.4 mmol) was added slowly and the reaction was allowed to stir at100° C. for about 4 hours. A precipitate formed upon cooling to RT. Theslurry was cooled to 0° C., filtered, washed with CH₃CN and air dried togive 345 mg of a tan solid identified as[2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridin-6-yl]-methanol.¹H NR (CDCl₃, 400 MHz): 2.62 (s, 3H), 2.63 (s, 3H), 4.74 (s, 2H), 7.01(d, 1H, J=5.5 Hz), 7.24 (d, 1H, J=7.7 Hz), 7.29 (d, 1H, J=7.29 Hz), 7.59(m, 2H), 7.71 (t, 1H, J=7.5 Hz), 8.29 (d, 1H, J=5.7 Hz), 9.40 (bs, 1H);MS (ESP+) 364.2 (M+1).

EXAMPLE 50[3-(2-Methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-6-yl]-methanol

4.0 N Sulfuric acid (0.12 mmol), catalytic sodium tungstate dihydrate,and 30 wt % hydrogen peroxide (9.8 mmol) was added to a slurry of[2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridin-6-yl]-methanol(0.95 mmol; see Example 49 for its preparation) in methanol (50 mL) at50° C. After 3.5 h the reaction was diluted with water (9.5 mL) andwarmed at 55° C. for a further 0.5 h. The reaction was then cooled toRT, quenched with saturated sodium thiosulfate, the pH adjusted to 6with 1M NaOH and filtered to give 0.208 g of a tan solid identified as[3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-6-yl]-methanol.¹H NMR (d₆-DMSO, 400 MHz): 2.40 (s, 3H), 3.52 (s, 3H), 4.57 (d, 2H,J=5.4 Hz), 7.32 (d, 1H, J=7.3 Hz), 7.54 (dd, 1H, J=1.3, 9.0 Hz), 7.87(m, 3H), 8.05 (d, 1H, J=5.2 Hz), 8.98 (d, 1H, J=5.4 Hz), 9.31 (bs, 1H);MS (ESP+) 400.2 (M+1).

EXAMPLE 51[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-6-yl]-methanol

In a sealed tube, a solution of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-6-yl]-methanol(0.526 mmol; see Example 50 for its preparation) and NH₄OAc (10.5 mmol)in 1:1 dioxane/water (7 mL) was warmed to 100° C. for 3 days. Themixture was cooled to RT, concentrated in vacuo and purified viapreparatory HPLC (5→50% CH₃CN/H₂O with 0.1% TFA) to yield 49.3 mg of ayellow solid identified as the TFA salt of[3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-6-yl]-methanol.¹H NMR (d₆-DMSO, 400 MHz): 2.530 (s, 3), 4.64 (s, 2H), 6.80 (d, 1H,J=6.0 Hz), 7.44 (d, 1H, J=8.6 Hz), 7.65 (bs, 1H), 7.67 (m, 1H), 7.79 (d,1H, J=8.0 Hz), 7.85 (d, 1H, J=9.3 Hz), 7.94 (dd, 1H, J=7.3, 7.3 Hz),8.24 (d, 1H, J=6.0 Hz), 9.42 (bs, 1H). MS (ESP+) 333.4 (M+1).

EXAMPLE 522-(6-Methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid methyl ester

Hydrogen bromide/acetic acid (30 wt %, 7.53 mmol) and 0.98 Mbromine/acetic acid (2.48 mmol) was added to a solution of1-(6-methyl-pyridin-2-yl)-2-(2-methylsulfanyl-pyrimidin-4-yl)-ethanone(1.911 mmol; see Example 1(b) for its preparation) and catalytic BHT inglacial acetic acid (10 mL) at RT with formation of a precipitate. After0.25 h the reaction was diluted to 100 mL with ether, filtered, washedwith ether, air dried briefly under a nitrogen stream and added to aflask containing 6-amino-nicotinic acid methyl ester (2.036 mmol) undera nitrogen atmosphere. Anhydrous acetonitrile (5 mL) anddiisopropylethylamine (7.65 mmol) were added and the resulting solutionwas warmed to 80° C. After 5.5 h the reaction was allowed to cool to RTand precipitate was formed. The slurry was filtered, washed withacetonitrile and air dried to give 0.4816 g of a tan solid identified asimpure2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid methyl ester. ¹H NMR (CDCl₃, 400 MHz) 2.35 (s, 3H), 2.69 (s, 3H),3.98 (s, 3H), 7.21 (d, J=5.26 Hz, 1H), 7.22 (d, J=6.81 Hz, 1), 7.73 (d,J=7.31 Hz, 1H), 7.82 (J=9.67 Hz, 1H), 7.94 (dd, J=9.36, 1.54 Hz, 1H),8.38 (d, J=5.33 Hz, 1H), 10.34 (s, 1H); MS (ESP+) 392.11 (M+1).

EXAMPLE 533-(2-Methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid methyl ester

4.0 N Sulfuric acid (0.02 mmol), catalytic sodium tungstate dihydrate,and 30 wt % hydrogen peroxide (0.88 mmol) was added to a slurry of2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid methyl ester (0.2664 mmol; see Example 52 for its preparation) in1:1 methanolmethylene chloride (4 mL) at 55° C. After 6.6 h, thereaction was diluted with water (2 mL) and warmed at 55° C. for 0.75 h.The reaction was then cooled to RT and neutralized to I₂/starch paperwith saturated sodium thiosulfate. The reaction was then diluted withmethylene chloride (20 mL) and the organic phase was washed with 10%sodium bicarbonate (5 mL) and brine (5 mL), dried (MgSO₄) andconcentrated in vacuo to give 0.1026 g of a yellow identified as3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid methyl ester. ¹H NMR (CDCl₃, 300 MHz) 2.54 (s, 3H), 3.45 (s, 3H),3.99 (s, 3H), 7.27 (d, J=6.60 Hz, 1H), 7.78 (d, J=9.30 Hz, 1H), 7.78(dd, J=7.80, 7.80 Hz, 1H), 7.90 (J=8.10 Hz, 1H), 8.01 (dd, J 9.30, 1.50Hz, 1H), 8.03 (d, J=5.40 Hz, 1H), 8.74 (d, J=5.40 Hz, 1H), 10.58 (s,1H); MS (ESP+) 424.15 (M+1).

EXAMPLE 543-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid methyl ester

A solution of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid methyl ester (0.1717 mmol; see Example 53 for its preparation) andammonium acetate (3.526 mmol) in 2:1 dioxane/water (3 mL) was warmed to100° C. in a sealed tube. After 23.5 h, the reaction was allowed to coolto RT, filtered, the solid washed with acetonitrile and air dried togive 0.0340 g of a tan solid. This solid was purified via reverse phaseHPLC (acetonitrile/water gradient with 0.1% TFA) to give 0.0295 g of ayellow solid identified as the TFA salt of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid methyl ester. ¹H NMR (DMSO-d6, 400 MHz) 2.41 (s, 3H), 3.87 (s, 3H),6.78 (d, J=5.69 Hz, 1H), 7.33 (d, J=7.44 Hz, 1H), 7.4 (br s, 2H),7.80-7.86 (m, 4H), 8.22 (d, J=5.65, 1H), 9.77 (s, 1H); MS (ESP+) 361.4(+1).

EXAMPLE 553-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid

In a sealed tube, a solution of3-(2-methylsulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid methyl ester (2.30 mmol; see Example 53 for its preparation) andNH₄OAc (45.8 mmol) in 1:1 dioxane/water (30 mL) was warmed to 100° C.for 3 days. The mixture was cooled to RT, resulting in a precipitatethat was filtered and washed with H₂0 to give 430 mg of the carboxylicacid and ester mixture. The mixture was dissolved in 2:1 THF/H₂0 (15mL), LiOH.H₂0 (5.95 mmol) was added and the reaction stirred at RT for0.5 h. The reaction was neutralized with 2M HCl, cooled to 0° C.,filtered and washed with H₂0 to give 370 mg of a solid identified as3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid. ¹H NMR (d₆-DMSO, 400 MHz): 2.39 (s, 3H), 6.75 (d, 1H J=5.3 Hz),6.79 (bs, 21), 7.30 (dd, 1H, J=4.0, 4.3 Hz), 7.83 (m, 5H), 8.29 (d, 1H,J=5.3 Hz), 9.65 (bs, 1H); MS (ESP+) 347.7 (M+1).

EXAMPLE 563-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid methoxy-amide

In a vial,3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid (0.144 mmol; see Example 55 for its preparation) was added with DMF(1 mL). The reaction was stirred until all material had dissolved. HATU(0.201 mmol) was then added making sure all material had dissolved. Thiswas followed by the addition of DIEA (1.15 mmol). This mixture wasallowed to stir for 10 min. Methoxyamine hydrochloride (0.173 mmol) wasthen added, the reaction was stirred for 2 h, concentrated in vacuo andpurified via preparative HPLC (5→50% CH₃CN:H₂0 with 0.1% TFA) to give28.9 mg of a solid identified as the TFA salt of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid methoxy-amide. ¹H NMR (d₆-DMSO, 400 MHz): 2.52 (s, 3H), 3.80 (s,3H), 6.92 (d, 1H, J=5.7 Hz), 7.45 (d, 1H, J=7.6 Hz), 7.61 (bs, 1H), 7.90(m, 5H), 8.32 (d, 1H, J=5.4 Hz), 9.69 (s, 1H); MS 376.5 (ESP+) (M+1).

EXAMPLE 573-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid ethylamide

In a vial,3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid (0.144 mmol; see Example 55 for its preparation) was added with DMF(1 mL). The reaction was stirred until all material had dissolved. HATU(0.201 mmol) was then added making sure all material had dissolved. Thiswas followed by the addition of DIEA (0.720 mmol). This mixture wasallowed to stir for 10 min. 2.0M Ethyl amine/THF (0.432 mmol) was thenadded, the reaction was stirred for 2 h, concentrated in vacuo andpurified via preparative HPLC (5→40% CH₃CN:H₂0 with 0.1% TFA) to give41.0 mg of a solid identified as the TFA salt of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid ethylamide. ¹H NMR (d₆-DMSO, 400 M[z): 1.17 (t, 3H, 7.3 Hz), 2.53(s, 3H), 3.37 (m, 2H), 6.92 (d, 1H, J=5.8 Hz), 7.44 (d, 1H, J=7.7 Hz),7.70 (bs, 1H), 7.93 (m, 4H), 8.33 (d, 1H, J=8.3 Hz), 8.73 (dd, 1H,J=5.4, 5.4 Hz), 9.71 (m, 1H); MS (ESP+) 374.3 (M+1).

EXAMPLE 583-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid (2-dimethylamino-ethyl)-amide

In a vial,3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid (0.144 mmol; see Example 55 for its preparation) was added with DMF(1 mL). The reaction was stirred until all material had dissolved. HATU(0.201 mmol) was then added making sure all material had dissolved. Thiswas followed by the addition of DIEA (0.720 mmol). This mixture wasallowed to stir for 10 min. N,N-Dimethylethyldiamine (0.173 mmol) wasthen added, the reaction was stirred for 2 h, concentrated in vacuo andpurified via preparative HPLC (5→40% CH₃CN:H₂0 with 0.1% TFA) to give29.9 mg of a solid identified as the TFA salt of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid (2-dimethylamino-ethyl)-amide. ¹H NMR (d₆-DMSO, 400 MHz): 2.50 (s,3H), 2.91 (d, 6H, J=4.6 Hz), 3.34 (q, 2H, J=5.5 Hz), 3.69 (q, 2H, J=5.7Hz), 6.90 (d, 1H, J=5.8 Hz), 7.41 (d, 1H, J=7.2 Hz), 7.51 (bs, 1H), 7.92(m, 4H), 8.33 (d, 1H, J=5.9 Hz), 8.96 (dd, 1H, J=5.7, 5.7 Hz), 9.60 (bs,1H), 9.78 (m, 1H); MS (ESP+) 417.5(M+1).

EXAMPLE 593-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid (2-methoxy-ethyl)-amide

In a vial,3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid (0.144 mmol; see Example 55 for its preparation) was added with DMF(1 mL). The reaction was stirred until all material had dissolved. HATU(0.201 mmol) was then added making sure all material had dissolved. Thiswas followed by the addition of DIEA (0.720 mmol). This mixture wasallowed to stir for 10 min. Methyoxyethylamine (0.288 mmol) was thenadded, the reaction was stirred for 2 h, concentrated in vacuo andpurified via preparative HPLC (5→40% CH₃CN:H₂0 with 0.1% TFA) to give36.1 mg of a solid identified as the TFA salt of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid (2-methoxy-ethyl)-amide. ¹H NMR (d₆-DMSO, 400 MHz): 2.51 (s, 3H),3.32 (s, 3H), 3.52 (m, 4H), 6.89 (d, 1H, J=5.6 Hz), 7.42 (d, 1H, J=8.1Hz), 7.45 (bs, 1H), 7.92 (m, 4H), 8.33 (d, 1H, J=5.6 Hz), 8.81 (m, 1H),9.70 (s, 1H): MS (ESP+) 404.7(M+1).

EXAMPLE 603-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid ([1,4]dioxan-2-ylmethyl)-amide

In a vial,3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid (0.144 mmol; see Example 55 for its preparation) was added with DMF(1 mL). The reaction was stirred until all material had dissolved. HATU(0.201 mmol) was then added making sure all material had dissolved. Thiswas followed by the addition of DIEA (0.720 mmol). This mixture wasallowed to stir for 10 min. [1,4]Dioxan-2-yl-methylamine (0.202 mmol)was then added, the reaction was stirred for 2 h, concentrated in vacuoand purified via preparative HPLC (5→40% CH₃CN:H₂0 with 0.1% TFA) togive 30.0 mg of a solid identified as the TFA salt of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid ([1,4]dioxan-2-ylmethyl)-amide. ¹H NMR (d₆-DMSO, 400 MHz): 2.52 (s,3H), 3.30 (m, 1H), 3.37 (m, 2H), 3.51 (m, 1H), 3.62 (m, 1H), 3.68 (m,1H), 3.73 (m, 1H), 3.80 (m, 2H), 6.92 (d, 1H, J=5.6 Hz), 7.43 (d, 1H,J=7.7 Hz), 7.59 (bs, 1H), 7.93 (m, 4H), 8.32 (d, 1H J=5.6 Hz), 8.82 (dd,1H, J=5.6, 5.6 Hz), 9.72 (s, 1H); MS (ESP+) 446.3 (M+1).

EXAMPLE 613-{[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carbonyl]-amino}-propionicacid methyl ester

In a vial,3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid (0.144 mmol; see Example 55 for its preparation) was added with DMF(1 mL). The reaction was stirred until all material had dissolved. HATU(0.201 mmol) was then added making sure all material had dissolved. Thiswas followed by the addition of DIEA (0.720 mmol). This mixture wasallowed to stir for 10 min. 3-Amino-propionic acid methyl ester (0.202mmol) was then added, the reaction was stirred for 2 h, concentrated invacuo and purified via preparative HPLC (5→40% CH₃CN:H₂O with 0.1% TFA)to give 27.3 mg of a solid identified as the TFA salt of3-{[3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carbonyl]-amino}-propionicacid methyl ester. ¹H NMR (d₆-DMSO, 400 MHz): 2.51 (s, 3H), 2.68 (t, 2H,J=7.4 Hz), 3.57 (q, 2H, J=6.8 Hz), 3.66 (s, 3H), 6.88 (d, 1H, J=5.4 Hz),7.42 (d, 1H, J=7.4 Hz), 7.43 (bs, 1H), 7.91 (m, 4H), 8.31 (d, 1H, J=6.0Hz), 8.84 (dd, 1H, J=5.4, 5.4 Hz), 9.71 (s, 1H; MS (ESP+) 432.2 (M+1).

EXAMPLE 623-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid ([1,4]dioxan-2-ylmethyl)-amide

In a vial,3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid (0.144 mmol; see Example 55 for its preparation) was added with DMF(1 mL). The reaction was stirred until all material had dissolved. HATU(0.201 mmol) was then added making sure all material had dissolved. Thiswas followed by the addition of DIEA (0.720 mmol). This mixture wasallowed to stir for 10 min. (unsym)-N,N-Dimethylhydrazine (0.202 mmol)was then added, the reaction was stirred for 2 h, concentrated in vacuoand purified via preparative HPLC (5→40% CH₃CN:H₂0 with 0.1% TFA) togive 9.8 mg of a solid identified as the TFA salt of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid ([1,4]dioxan-2-ylmethyl)-amide. ¹H NMR (d₆-DMSO, 400 MHz): 2.52 (s,3H), 2.74 (s, 6H), 6.92 (d, 1H, J=5.6 Hz), 7.43 (d, 1H, J=7.4 Hz), 7.57(bs, 1H), 7.92 (m, 4H), 8.32 (d, 1H, J=5.6 Hz), 9.70 (s, 1H); MS (ESP+)389.2 (M+1).

EXAMPLE 63N-[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carbonyl]-methanesulfonamide

In a vial,3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid (60 mg, 0.173 mmol; see Example 55 for its preparation) was addedwith DMF (1 mL). The reaction was stirred until all material haddissolved. HATU (92 mg, 0.242 mmol) was then added making sure allmaterial had dissolved. This was followed by the addition of DIEA (150uL, 0.865 mmol). This mixture was allowed to stir for 10 min.Methylsulfonamine (20 mg, 0.207 mmol) was then added and the reactionwas stirred for 2 h and checked by HPLC. The reaction was purified bypreparative HPLC (5→40% CH3 CN:H20 with 0.1% TFA). (Impurity in NMR) ¹HNMR (d₆-DMSO, 400 MHz): 2.47 (s, 3H), 3.45 (s, 3H), 6.88 (d, 1H, J=5.7Hz), 7.17 (bs, 1H), 7.36 (dd, 1H, J=2.8, 5.7 Hz), 7.88 (m, 4H), 8.34 (d,1H, J=5.0 Hz), 9.81 (s, 1H). MS (ESP+) 424.3 (M+1).

EXAMPLE 643-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid (2-thiophen-2-yl-ethyl)-amide

In a vial,3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid (50 mg, 0.144 mmol; see Example 55 for its preparation) was addedwith DMF (1 mL). The reaction was stirred until all material haddissolved. HATU (77 mg, 0.201 mmol) was then added making sure allmaterial had dissolved. This was followed by the addition of DIEA (180uL, 0.720 mmol). This mixture was allowed to stir for 10 min.2-Thiophen-2-yl-ethylamine (21 uL, 0.173 mmol) was then added and thereaction was stirred for 2 h and checked by HPLC. The reaction waspurified by preparative HPLC (5→40% CH3CN:H20 with 0.1% TFA). ¹H NMR(d₆-DMSO, 400 MHz): 2.52 (s, 3H), 3.14 (t, 2H, J=6.4 Hz), 3.58 (q, 2H,J=6.4 Hz), 6.92 (d, 1H, J=5.7 Hz), 7.00 (m, 3H), 7.39 (dd, 1H, J=1.3,5.0 Hz), 7.44 (d, 1H, J=8.0 Hz), 7.54 (bs, 1H), 7.94 (m, 4H), 8.34 (d,1H, J=6.0 Hz), 8.90 (dd, 1H, J=5.3, 5.7 Hz), 9.70 (s, 1H). MS (ESP+)456.1 (M+1).

EXAMPLE 653-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid cyclopropylamide

In a vial,3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylicacid (50 mg, 0.144 mmol; see Example 55 for its preparation) was addedwith DMF (1 mL). The reaction was stirred until all material haddissolved. HATU (77 mg, 0.201 mmol) was then added making sure allmaterial had dissolved. This was followed by the addition of DIEA (180uL, 0.720 mmol). This mixture was allowed to stir for 10 min.Cyclopropylamine (12 uL, 0.173 mmol) was then added and the reaction wasstirred for 2 h and checked by HPLC. The reaction was purified bypreparative HPLC (5→40% CH₃CN:H2O with 0.1% TFA). ¹H NMR (d₆-DMSO, 400MHz): 0.65 (m, 2H), 0.78 (m, 2H), 2.51 (s, 3H), 2.92 (m, 1H), 6.94 (d,1H, J=6.0 Hz), 7.45 (d, 1H, J=7.4 Hz), 7.73 (bs, 1H), 7.93 (m, 4H), 8.33(d, 1H, J=6.3 Hz), 8.72 (d, 1H, J=4.0 Hz), 9.70 (s, 1H). MS (ESP+) 386.4(M+1).

EXAMPLE 664-[6-Methyl-2-(6-methyl-pyridin-2-yl)-8-morpholin-4-yl-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ol

A mixture of4-[8-bromo-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ol(30 mg, 0.08 mmol; see Example 67 for its preparation), morpholine (15ul, 0.17 mmol), Pd(OAc)₂ (9 mg, 0.04 mmole), NaOtBu (19 mg, 0.198) and2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (20 mg, 0.05mmol) in dioxane (600 ul) was degassed under N₂. The reaction was heated(105° C.) for 1.5 h. The mixture was diluted with CH₂Cl₂ (2 mL) andfiltered through celite. The solvent was removed invacuo. The residuewas purified by HPLC (C18, H₂O:MeCN gradient) to afford the titledcompound as a red solid (3.1 mg, 10%) ¹H NMR (300 MHz, CDCl₃) 8.82 (s,J=6.6 Hz 1H), 8.50 (d, J=8.1 Hz, 1H), 8.19 (s, 1H), 7.80 (t, J=8.1 Hz,1H), 7.52(d, J=7.4 Hz, 1H), 7.03 (d, J=6.9 Hz, 1H) 6.69 (s, 1H) 4.05(m,4H), 3.65 (m, 4H) 3.03 (s, 3H), 2.47(s, 3H); MS (ESP+) 403 (M+1).

EXAMPLE 674-[8-Bromo-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ol

A mixture of8-bromo-3-(2-methanesulfonyl-pyrimidin-4-yl)-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine(877 mg, 1.91 mmol; prepared in accordance with Ex. 2), NH₄OAc (3 g),H₂O (3 mL and dioxane (10 mL) in DMSO (11 mL) was refluxed (12 h). Thesolvent was removed in vacuo. The residue was triturated with water toafford the titled compound as a yellow solid (682 mg, 90%). ¹H NMR (300MHz, DSMO-d₆) 9.30 (s, 1H), 7.84 (m, 5H), 7.33 (d, J=7.0 Hz, 1H), 6.31(d, J=6.0 Hz, 1H), 2.45 (s, 3H), 2.37 (s, 3H); MS (ESP+) 396 (M+1).

EXAMPLE 684-[6-Methyl-2-(6-methyl-pyridin-2-yl)-8-(2-pyridin-3-yl-ethylamino)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ol

A mixture of4-[8-bromo-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ol(50 mg, 0.13 mmol; see Example 67 for its preparation),2-pyridin-3-yl-ethylamine (34 mg, 0.28 mmol), Pd(OAc)₂ (15 mg, 0.07mmol), NaOtBu (32 mg, 0.33 mmol) and2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (33 mg, 0.084mmol) in dioxane (1 mL) was degassed under N₂. The reaction was heated(160° C.) in a microwave for 30 min. The mixture was diluted with CH₂Cl₂(2 mL) and MeOH (100 ul) and passed through a plug of SiO₂. The residuewas purified by HPLC (C18, H₂O:MeCN gradient (10 mM NH₄HCO₃ buffer)) toafford the titled compound as a red solid (5 mg, 9%). MS (ESP+) 438(M+1).

EXAMPLE 694-[6-Methyl-2-(6-methyl-pyridin-2-yl)-8-(2-pyridin-2-yl-ethylamino)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ol

A mixture of4-[8-bromo-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ol(50 mg, 0.13 mmol; see Example 67 for its preparation),2-pyridin-2-yl-ethylamine (34 mg, 0.28 mmol), Pd(OAc)₂ (15 mg, 0.07mmol), NaOtBu (32 mg, 0.33 mmol) and2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (33 mg, 0.084mmol) in dioxane (1 mL) was degassed under N₂. The reaction was heated(160° C.) in a microwave for 30 min. The mixture was diluted with CH₂Cl₂(2 mL) and MeOH (100 ul) and passed through a plug of SiO₂. The residuewas purified by HPLC (C18, H₂O:MeCN gradient (10 mM NH₄HCO₃ buffer)) toafford the titled compound as yellow solid (3 mg, 5%). ¹H NMR (300 MHz,CDCl₃) 8.63 (s, J=4.2 Hz 1H), 7.79 (d, J=7.9 Hz, 1H), 7.64 (td, J 7.9,2.0 Hz, 1H), 7.22 (m, 2H), 6.61 (s, 1H), 6.23 (s, 1H), 5.70 (s, 1H),5.32 (s, 1H), 3.73 (q, J=6.4 Hz, 2H), 3.24 (t, J=6.4 Hz, 2H), 2.87 (s,3H), 2.35 (s, 3H); MS (ESP+) 438 (M+1).

EXAMPLE 704-[6-Methyl-2-(6-methyl-pyridin-2-yl)-8-(2-pyridin-4-yl-ethylamino)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ol

A mixture of4-[8-bromo-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ol(50 mg, 0.13 mmol; see Example 67 for its preparation),2-pyridin-4-yl-ethylamine (34 mg, 0.28 mmol), Pd(OAc)₂ (15 mg, 0.07mmol), NaOtBu (32 mg, 0.33 mmol) and2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (33 mg, 0.084mmol) in dioxane (1 mL) was degassed under N₂. The reaction was heated(160° C.) in a microwave for 30 min. The mixture was diluted with CH₂Cl₂(2 mL) and MeOH (100 ul) and passed through a plug of SiO₂. The residuewas purified by HPLC (C18, H₂O:MeCN gradient (10 mM NH₄HCO₃ buffer)) toafford the titled compound as yellow solid (2 mg, 4%). ¹H NMR (300 MHz,CDCl₃) 8.57 (m, 2H), 7.9 (s, 1H), 7.79 (t, J=7.6 Hz, 1H), 7.23 (m, 3H),6.59 (d, J=6.0, 1H), 6.21 (s, 1H), 5.39 (t, J=6.1 Hz, 1H), 3.64 (q,J=7.0 Hz, 2H), 3.08 (t, J=7.0 Hz, 2H), 2.84 (s, 3H), 2.37 (s, 3H); MS(ESP+) 438 (M+1).

EXAMPLE 714-[6-Methyl-2-(6-methyl-pyridin-2-yl)-8-(2-morpholin-4-yl-ethylamino)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ol

A mixture of4-[8-bromo-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ol(50 mg, 0.13 mmol; see Example 67 for its preparation),2-morpholin-4-yl-ethylamine (36 mg, 0.28 mmol), Pd(OAc)₂ (15 mg, 0.07mmol), NaOtBu (32 mg, 0.33 mmol) and2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (33 mg, 0.084mmol) in dioxane (1 mL) was degassed under N₂. The reaction was heated(160° C.) in a microwave for 30 min. The mixture was diluted with CH₂Cl₂(2 mL) and MeOH (100 ul) and passed through a plug of SiO₂. The residuewas purified by HPLC (C18, H₂O:MeCN gradient (10 mM NH₄HCO₃ buffer)) toafford the titled compound as yellow solid (4.5 mg, 8%). ¹H NMR (300MHz, CDCl₃) 8.11 (br.s, 1H), 7.80 (t, J=7.7 Hz, 1H), 7.26 (d, J=8.4 Hz,1H), 6.61 (d, J=6.50, 1H), 6.22 (s, 1H), 3.84 (m, 4H), 3.48 (t, J=5.5Hz, 2H), 2.89 (t, J=6.1 Hz, 2H), 2.86 (s, 3H), 2.69 (s, 4H) 2.36(s 3H);MS (ESP+) 446 (M+1).

EXAMPLE 72[3-(2-Amino-pyrimidin-4-yl)-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-8-yl]-(3-morpholin-4-yl-propyl)-amine

A mixture of4-[8-bromo-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine(50 mg, 0.13 mmol), 3-morpholin-4-yl-propylamine (35 mg, 0.28 mmol),Pd(OAc)₂ (15 mg, 0.07 mmol), NaOtBu (32 mg, 0.33 mmol), H₂O (5 μL) and2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (33 mg, 0.084mmol) in dioxane (1 mL) was degassed under N₂. The reaction was heated(160° C.) for 1 h. The reaction was filtered through celite. The residuewas purified by HPLC (C18, H₂O:MeCN gradient (10 mM NH₄HCO₃ buffer)) toafford the titled compound as yellow solid (5 mg, 8%). ¹H NMR (300 MHz,CDCl₃) 8.42 (s, 1H), 8.14 (d, J=5.1 Hz, 1H), 7.63 (t, J=7.8 Hz, 1H),7.55 (d, J=7.1 Hz, 1H), 7.14 (d, J=7.8 Hz, 1H), 6.67 (d, J=5.1 Hz, 1H),6.12 (s, 1H), 5.79 (t, J=5.5 Hz, 1H), 5.11 (s, 1H), 3.8 (m, 4H), 3.36(q, J=6.3 Hz, 2H), 2.58 (s, 3H), 2.53 (t, J=7.1 Hz, 2H), 2.49 (m, 4H),2.31 (s, 3H), 1.92 (quint, J=6.7 Hz, 2H); MS (ESP+) 459 (M+1).

EXAMPLE 73[3-(2-Amino-pyrimidin-4-yl)-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-8-yl]-(2-morpholin-4-yl-ethyl)-amine

A mixture of4-[8-bromo-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine(50 mg, 0.13 mmol), 2-morpholin-4-yl-ethylamine (32 mg, 0.28 mmol),Pd(OAc)₂ (15 mg, 0.07 mmol), NaOtBu (32 mg, 0.33 mmol), H₂O (5 μL) and2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (33 mg, 0.084mmol) in dioxane (1 mL) was degassed under N₂. The reaction was heated(160° C.) for 1 h. The reaction was filtered through celite. The residuewas purified by HPLC (C18, H₂O:MeCN gradient (10 mM NH₄HCO₃ buffer)) toafford the titled compound as red solid (6 mg, 10%). ¹H NMR (300 MHz,CDCl₃) 8.44 (s, 1H), 8.15 (d, J=5.0 Hz, 1H), 7.63 (t, J=7.6 Hz, 1H),7.55 (d, J=7.4 Hz, 1H), 7.15 (d, J=7.7 Hz, 1H), 6.66 (d, J=5.5 Hz, 1H),6.12 (s, 1H), 5.57 (t, J=5.3 Hz, 1H), 5.11 (s, 1H), 3.76 (m, 4H), 3.37(q, J=6.1 Hz, 2H), 2.74 (t, J=6.3 Hz, 2H), 2.59 (s, 3H), 2.54 (m, 4H),2.31 (s, 3H); MS (ESP+) 445 (M+1).

EXAMPLE 744-[6-Methyl-2-(6-methyl-pyridin-2-yl)-8-morpholin-4-yl-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine

A mixture of4-[8-bromo-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine(50 mg, 0.13 mmol), morpholine (25 μL, 0.29 mmol), Pd(OAc)₂ (15 mg, 0.07mmol), NaOtBu (32 mg, 0.33 mmol), H₂O (5 μL) and2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (33 mg, 0.084mmol) in dioxane (1 mL) was degassed under N₂. The reaction was heated(160° C.) for 1 h. The reaction was filtered through celite. The residuewas purified by HPLC (C18, H₂O:MeCN gradient (10 mM NH₄HCO₃ buffer)) toafford the titled compound as red solid (2.9 mg, 6%). ¹H NMR (300 MHz,CDCl₃) 8.70 (s, 1H), 8.15 (d, J=5.5 Hz, 1H), 7.79 (d, J=7.8 Hz, 1H),7.67 (t, J=7.8 Hz, 1H), 7.14 (d, J=7.6 Hz, 1H), 6.84 (d, J=5.5 Hz, 1H),6.46 (s, 1), 5.23 (s, 2H), 4.01 (m, 4H), 3.59 (m, 4H), 2.5 (s, 3H), 2.35(s, 3H); MS (ESP+) 402 (M+1).

EXAMPLE 75[3-(2-Amino-pyrimidin-4-yl)-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-8-yl]-(2-pyridin-3-yl-ethyl)-amine

A mixture of4-[8-bromo-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine(50 mg, 0.13 mmol), 2-pyridin-3-yl-ethylamine (33 mg, 0.29 mmol),Pd(OAc)₂ (15 mg, 0.07 mmol), NaOtBu (32 mg, 0.33 mmol), H₂O (5 μL) and2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (33 mg, 0.084mmol) in dioxane (1 mL) was degassed under N₂. The reaction was heated(160° C.) for 1 h. The reaction was filtered through celite. The residuewas purified by HPLC (C18, H₂O:MeCN gradient (10 mM NH₄HCO₃ buffer)) toafford the titled compound as red solid (6.5 mg, 11%). ¹H NMR (300 MHz,CDCl₃) 8.57 (d, J=2.1, 1H), 8.51 (dd, J=4.8, 1.6 Hz, 1H), 8.46 (s, 1H),8.12 (d, J=5.4 Hz, 1H), 7.63 (m, 2H), 7.56 (d, J=7.5 Hz, 1H), 7.26 (dd,J=8.1, 4.8 Hz, 1H), 7.16 (d, J=7.5 Hz, 1H), 6.67 (d, J=5.4 Hz, 1H), 6.14(s, 1H), 5.50 (s, 1H), 5.37 (s, 2H), 3.57 (q, J=7.5 Hz, 2H), 3.05 (t,J=7.5 Hz, 2H), 2.59 (s, 3H), 2.32 (s, 3H); MS (ESP+) 437 (M+1).

EXAMPLE 76[3-(2-Amino-pyrimidin-4-yl)-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-8-yl]-(2-pyridin-2-yl-ethyl)-amine

A mixture of4-[8-bromo-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine(50 mg, 0.13 mmol), 2-pyridin-2-yl-ethylamine (33 mg, 0.29 mmol),Pd(OAc)₂ (15 mg, 0.07 mmol), NaOtBu (32 mg, 0.33 mmol), H₂O (5 μL) and2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (33 mg, 0.084mmol) in dioxane (1 mL) was degassed under N₂. The reaction was heated(160° C.) for 1 h. The reaction was filtered through celite. The residuewas purified by HPLC (C18, H₂O:MeCN gradient (10 mM NH₄HCO₃ buffer)) toafford the titled compound as red solid (2.6 mg, 5%). ¹H NMR (300 MHz,CDCl₃) 8.61 (d, J=4.9, 1H), 8.46 (s, 1H), 8.06 (d, J=6 Hz, 1H), 7.66 (m,3H), 7.18 (m, 2H), 6.71 (d, J=6.1 Hz, 1H), 6.28 (s, 1H), 5.80 (s, 2H),3.75 (t, J=7.3 Hz, 2H), 3.25 (t, J=7.3 Hz, 2H), 2.58 (s, 3H), 2.33 (s,3H); MS (ESP+) 437 (M+1).

EXAMPLE 77(3-(2-Amino-pyrimidin-4-yl)-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-8-yl]-(2-pyridin-4-yl-ethyl)-amine

A mixture of4-[8-bromo-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine(50 mg, 0.13 mmol), 2-pyridin-4-yl-ethylamine (33 mg, 0.29 mmol),Pd(OAc)₂ (15 mg, 0.07 mmol), NaOtBu (32 mg, 0.33 mmol), H₂O (5 μL) and2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (33 mg, 0.084mmol) in dioxane (1 mL) was degassed under N₂. The reaction was heated(160° C.) for 1 h. The reaction was filtered through celite. The residuewas purified by HPLC (C18, H₂O:MeCN gradient (10 mM NH₄HCO₃ buffer)) toafford the titled compound as red solid (6 mg, 11%). ¹H NMR (300 MHz,CDCl₃) 8.55 (m, 2H), 8.46 (s, 1H), 8.11 (d, J=6 Hz, 1H), 7.66 (t, J=7.8Hz, 1H), 7.58 (d, J=8.4 Hz, 1H), 7.23 (m, 2H), 7.18 (d, J=7.8 Hz, 1H),6.67 (d, J=5.4 Hz, 1H), 6.17 (s, 1H), 5.6 (s, 1H), 5.46 (s, 2H), 3.59(q, J=6.6 Hz, 2H), 3.06 (t, J=7.2 Hz, 211), 2.58 (s, 3H), 2.33 (s, 3H);MS (ESP+) 437 (M+1).

EXAMPLE 782-(6-Methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid ethyl ester

Hydrogen bromide/acetic acid (30 wt %, 40.11 mmol) and 1.00 Mbromine/acetic acid (8.02 mmol) was added to a solution of1-(6-methyl-pyridin-2-yl)-2-(2-methylsulfanyl-pyrimidin-4-yl)-ethanone(6.17 mmol; see Example 1(b) for its preparation) and catalytic BHT inglacial acetic acid (29.6 mL) at RT to form a precipitate. After 0.3 hthe reaction was diluted to 400 mL with ether, filtered, washed withether, dried briefly under N₂ gas to give an orange solid. The solid wasadded to a flask containing 2-amino-isonicotinic acid ethyl ester (6.17mmol). Toluene (20 mL) was added and the slurry was heated to 100° C.Diisopropylethylamine (24.68 mmol) was added dropwise. After 3.3 h thereaction was allowed to cool to 0° C. and precipitate was formed. Theslurry was filtered, the solid washed with acetonitrile and air dried togive 1.160 g of a solid identified as2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid ethyl ester. ¹H NMR (CDCl₃, 300 MHz): 1.44 (t, J=7.4, 3H), 2.54 (s,3H), 2.64 (s, 3H), 4.49 (q, J=7.0, 2H), 7.21 (dd, J=7.4, 1.3 Hz, 1H),7.23 (d, J=5.4 Hz, 1H), 7.54 (dd, J=7.4, 1.4 Hz, 1H), 7.73 (m, 2H), 8.41(d, J=5.4 Hz, 1H), 8.45 (dd, J=1.7, 0.8 Hz, 1H), 9.46 (dd, J=7.4, 0.8Hz, 1H); MS (ESP+) 406.4 (M+1).

EXAMPLE 793-(2-Methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid ethyl ester

4.0 N Sulfuric acid (0.33 mmol), catalytic sodium tungstate dihydrate,and 30 wt % hydrogen peroxide (9.44 mmol) were added to a slurry of2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid ethyl ester (2.86 mmol; see Example 78 for its preparation) in 1:1ethanol/dichloromethane (25 mL) at 55° C. After 5.25 h, the reaction wasdiluted with water (25 mL) and warmed at 55° C. for an additional 1 h.The reaction was then cooled to RT, quenched with saturated sodiumthiosulfate and then extracted with dichloromethane (300 mL). Theorganic phase was washed with saturated sodium bicarbonate (125 mL) andbrine (125 mL), dried (Na₂SO₄) and concentrated in vacuo to give 1.264 gof a solid identified as3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid ethyl ester. ¹H NMR (CDCl₃, 300 MHz): 1.45 (t, J=7.2 Hz, 3H), 2.53(s, 3H), 3.40 (s, 3H), 4.46 (q, J=7.2 Hz, 2H), 7.26 (d, J=7.6 Hz, 1H),7.67 (dd, J=7.4, 1.8 Hz, 1H), 7.78 (t, J=7.6 Hz, 1H), 7.91 (d, J=7.6 Hz,1H), 8.00, (d, J=5.4 Hz, 1H), 8.48 (m, 1H), 8.72 (d, J=5.4 Hz, 1H), 9.70(d, J=7.4 Hz, 1H); MS (ESP+) 438.4 (M+1).

EXAMPLE 803-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid ethyl ester

A solution of3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid ethyl ester (6.35 mmol; see Example 79 for its preparation) andammonium acetate (190.50 mmol) in 2:1 dioxane/water (84 mL) was warmedto 100° C. for 5 days. The reaction solution was then concentrated invacuo, diluted with water (˜100 mL) to give a precipitate that wasfiltered, washed with water and air dried to give 2.035 g of a solididentified as3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid ethyl ester. ¹H NMR (CDCl₃, 300 MHz): 1.44 (t, J=7.2 Hz, 3H), 2.56(s, 3H), 4.44 (q, J=7.2 Hz, 2H), 6.81 (d, J=5.4 Hz, 1H), 7.19 (m, 1H),7.50 (d, J=7.3 Hz, 1H), 7.68 (m, 2H), 8.17 (d, J=5.4 Hz, 1H), 8.44 (m,1H), 9.40 (d, J=7.3 Hz, 1H); MS (ESP+) 375.3 (M+1).

EXAMPLE 813-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid

Lithium hydroxide monohydrate (0.967 mmol) was added to a solution of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid ethyl ester (0.134 mmol; see Example 80 for its preparation) in 2:1tetrahydrofuran/water (2.7 mL). After 2 h, the reaction was concentratedin vacuo to remove the organic phase, diluted with water (˜3 mL) andacidified to pH 5 with 10% HCl. The reaction was cooled to 0° C. to givea precipitate that was filtered, washed with water and air dried. Theresulting solid was purified via reverse phase HPLC (acetonitrile/watergradient with 0.1% TFA) to give 33 mg of a yellow solid identified asthe tri-TFA salt of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid. ¹H (d6-DMSO, 300 MHz): 2.42 (s, 3H), 6.59 (d, J=5.3 Hz, 1H), 6.76(s, 2H), 7.27 (d, J=7.3 Hz, 1H), 7.46 (dd, J=7.3, 1.7 Hz, 1H, 7.73 (d,J=7.8 Hz, 1H), 7.81 (t, J=7.8 Hz, 1H), 8.06 (m, 1H), 8.16 (d, J=5.3 Hz,1H), 9.37 (d, J=7.2 Hz, 1H); MS (ESP+) 347.5 (M+1).

EXAMPLE 82N-[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carbonyl]-methanesulfonamide

HATU (0.405 mmol), diisopropylethylamine (1.445 mmol) andmethanesulfonamide (0.347 mmol) were added to a slurry of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid (0.289 mmol; see Example 81 for its preparation) inN,N-dimethylformamide (2.9 mL) at RT. After 0.7 h, HATU (0.405 mmol),diisopropylethylamine (1.445 mmol) and methanesulfonamide (0.347 mmol)were added and the reaction was stirred at RT for an additional 2.75 h.The reaction was concentrated in vacuo and purified via reverse phaseHPLC (acetonitrile/water gradient with 0.1% TFA) to give 65 mg of ayellow solid identified as the tri-TFA salt ofN-[3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carbonyl]-methanesulfonamide.¹H (d6-DMSO, 300 MHz): 3.44 (s, 3H), 6.82 (d, J=6.0 Hz, 1H), 7.44 (d,J=7.8 Hz, 1H), 7.56 (dd, J=7.4, 1.8 Hz, 1H), 7.82 (bs, 2H), 7.86 (d,J=7.8 Hz, 1H), 7.95 (t, J=7.8 Hz, 1H), 8.25 (d, J=6.0 Hz, 1H), 8.49 (m,1H), 9.62 (d, J=7.4 Hz, 1H); MS (ESP+) 424.11 (M+1); MS (ESP−) 422.14(M−1).

EXAMPLE 833-(2-Amino-pyrimidin-4-yl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid cyclopropylamide

HATU (0.304 mmol), diisopropylethylamine (1.085 mmol) andcyclopropylamine (0.260 mmol) were added to a slurry of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid (0.217 mmol; see Example 81 for its preparation) inN,N-dimethylformamide (2.2 mL) at RT. After 3.25 h, the reaction wasconcentrated in vacuo and purified via reverse phase HPLC(acetonitrile/water gradient with 0.1% TFA) to give 81 mg of a yellowsolid identified as the tri-TFA salt of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid cyclopropylamide. ¹H (d6-DMSO, 300 MHz): 0.64 (m, 2H), 0.75 (m,2H), 2.50 (s, 3H), 2.91 (m, 1H), 6.82 (d, J=6.1 Hz, 1H), 7.20 (bs, 2H),7.43 (d, J=7.7 Hz, 1H), 7.54 (dd, J=7.5, 1.6 Hz, 1H), 7.83 (d, J=7.4 Hz,1H), 7.94 (t, J=7.7 Hz, 1H), 8.22 (d, J=6.2 Hz, 1H), 8.29 (m, 1H), 8.82(d, J=4.0 Hz, 1H), 9.62 (d, J=7.4 Hz, 1H); MS (ESP+) 386.5 (M+1).

EXAMPLE 843-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid (2-thiophen-2-yl-ethyl)-amide

HATU (0.202 mmol), diisopropylethylamine (0.720 mmol) and2-thiopheneethylamine (0.173 mmol) were added to a slurry of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid (0.144 mmol; see Example 81 for its preparation) inN,N-dimethylformamide (1.4 mL) at RT. After 18 h, the reaction wasconcentrated in vacuo and purified via reverse phase HPLC(acetonitrile/water gradient with 0.1% TFA) to give 81 mg of a yellowsolid identified as the tri-TFA salt of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid (2-thiophen-2-yl-ethyl)-amide. ¹H (d6-DMSO, 300 MHz): 2.50 (s, 3H),3.13 (t, J=6.6 Hz, 2H), 3.57 (m, 2H), 6.83 (d, J=6.1 Hz, 1H), 6.96 (m,2H), 7.36 (m, 1H), 7.44 (d, J=7.8 Hz, 1H), 7.55 (d, J=7.4 Hz, 1H), 7.85(d, J=7.9 Hz, 1H), 7.96 (t, J=7.9 Hz, 1H), 8.23 (d, J=6.2 Hz, 1H), 8.30(m, 1H), 9.04 (m, 1H), 9.61 (d, J=7.3 Hz, 1H); MS (ESP+) 456.22 (M+1).

EXAMPLE 853-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid ethylamide

HATU (0.202 mmol), diisopropylethylamine (0.720 mmol) and ethylamine(0.173 mmol) were added to a slurry of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid (0.144 mmol; see Example 81 for its preparation) inN,N-dimethylformamide (1.4 mL) at RT. After 20 h, the reaction wasconcentrated in vacuo and purified via reverse phase HPLC(acetonitrile/water gradient with 0.1% TFA) to give 59 mg of a yellowsolid identified as the tri-TFA salt of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid ethylamide. ¹H (d6-DMSO, 300 MHz): 1.18 (t, J=7.2 Hz, 3H), 2.50 (s,3H), 3.36 (m, 2H), 6.84 (d, J=6.2 Hz, 1H), 7.45 (d, J=7.8 Hz, 1H), 7.57(dd, J=7.4, 1.9 Hz, 1H), 7.85 (d, J=7.8 Hz, 1H), 7.96 (t, J=7.8 Hz, 1H),8.22 (d, J=6.2 Hz, 1H), 8.31 (m, 1H), 8.88 (t, J=5.6 Hz, 1H), 9.65 (d,J=7.4 Hz, 1H); MS (ESP+) 374.21 (I+1).

EXAMPLE 863-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid methoxy-amide

HATU (0.202 mmol), diisopropylethylamine (1.008 mmol) and methoxylaminehydrochloride (0.173 mmol) were added to a slurry of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid (0.144 mmol; see Example 81 for its preparation) inN,N-dimethylformamide (1.4 mL) at RT. After 20 h, the reaction wasconcentrated in vacuo and purified via reverse phase HPLC(acetonitrile/water gradient with 0.1% TFA) to give 59 mg of a yellowsolid identified as the tri-TFA salt of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid methoxy-amide. ¹H (d6-DMSO, 300 MHz): 2.50 (s, 3H), 3.78 (s, 3H),6.78 (d, J=5.9 Hz, 1H), 7.41 (m, 2H), 7.55 (bs, 2H), 7.82 (d, J=7.5 Hz,1H), 7.92 (t, J=7.8 Hz, 1H), 8.16 (m, 1H), 8.22 (d, J=5.9 Hz, 1H), 9.59(d, J=7.8 Hz, 1H), 12.15 (bs, 1H); MS (ESP+) 376.17 (M+1).

EXAMPLE 873-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid (2-amino-ethyl)-amide

HATU (0.202 mmol), diisopropylethylamine (0.720 mmol) andN-(2-aminoethyl)carbamic acid tert-butyl ester (0.173 mmol) were addedto a slurry of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid (0.144 mmol; see Example 81 for its preparation) inN,N-dimethylformamide (1.4 mL) at RT. After 18 h, the reaction wasconcentrated in vacuo and was then dissolved in 1:1 dichloromethane/TFA(1 mL) at RT. After 2 h, the reaction was concentrated in vacuo andpurified via reverse phase HPLC (acetonitrile/water gradient with 0.1%TFA) to give 17 mg of a yellow solid identified as the tri-TFA salt of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid (2-amino-ethyl)-amide. ¹H (d6-DMSO, 400 MHz): 2.46 (s, 3H), 3.05(q, J=5.9 Hz, 21), 3.57 (dt, J=5.9, 5.9 Hz, 2H), 6.74 (d, J=5.8 Hz, 1H),7.37 (d, J=7.8 Hz, 1H), 7.50 (dd, J=7.4, 1.8 Hz, 1H), 7.82 (d, J=7.6 Hz,1H), 7.85 (bs, 2H), 7.89 (d, J=7.7 Hz, 1H), 8.22 (d, J=5.8 Hz, 1H), 8.32(dd, J=1.7, 0.8 Hz, M1), 8.97 (t, J=5.7 Hz, 1H), 9.58 (dd, J=7.4, 0.7Hz, 1H); MS (ESP+) 389.21 (M+1).

EXAMPLE 883-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid (piperidin-3-ylmethyl)-amide

HATU (0.202 mmol), diisopropylethylamine (0.720 mmol) and(3-aminomethyl)-1-N-Boc-piperdine (0.173 mmol) were added to a slurry of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid (0.144 mmol; see Example 81 for its preparation) inN,N-dimethylformamide (1.4 mL) at RT. After 18 h, the reaction wasconcentrated in vacuo and was then dissolved in 1:1 dichloromethane/TFA(1 mL) at RT. After 2 h, the reaction was concentrated in vacuo andpurified via reverse phase HPLC (acetonitrile/water gradient with 0.1%TFA) to give 32 mg of a yellow solid identified as the tri-TFA salt of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid (piperidin-3-ylmethyl)-amide. ¹H (d6-DMSO, 400 MHz): 1.37 (q,J=12.2 Hz, 2H), 1.86 (d, J=13.9 Hz, 3H), 2.46 (s, 3H), 2.87 (q, J=11.3Hz, 2H), 3.28 (m, 4H), 6.73 (d, J=5.8 Hz, 1H), 7.27 (bs, 1H), 7.36 (d,J=7.8 Hz, 1H), 7.48 (dd, J=7.4, 1.8 Hz, 1H), 7.79 (d, J=7.8 Hz, 1H),7.88 (t, J=7.8 Hz, 1H), 8.17 (bs, 1H), 8.21 (d, J=5.8 Hz, 1H), 8.29 (m,1H), 8.50 (bs, 1H), 8.92 (t, J=6.0 Hz, 1H), 9.55 (d, J=7.4 Hz, 1H); MS(ESP+) 443.16 (M+1).

EXAMPLE 893-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid 2,2-dimethylhydrazide

HATU (0.202 mmol), diisopropylethylamine (0.720 mmol) andunsym-dimethylhydrazine (0.173 mmol) were added to a slurry of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid (0.144 mmol; see Example 81 for its preparation) inN,N-dimethylformamide (1.4 mL) at RT. After 15 h, the reaction wasconcentrated in vacuo and purified via reverse phase HPLC(acetonitrile/water gradient with 0.1% TFA) to give 31 mg of a yellowsolid identified as the tri-TFA salt of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid 2,2-dimethylhydrazide. ¹H (d6-DMSO, 400 MHz): 2.50 (s, 3H), 2.71(s, 6H), 6.81 (d, J=5.9 Hz, 1), 7.42 (d, J=7.8 Hz, 1H), 7.49 (d, J=7.5Hz, 1H), 7.69 (bs, 2H), 7.83 (d, J=7.8 Hz, 1H), 7.94 (t, J=7.8 Hz, 1H),8.22 (d, J=5.9 Hz, 1H), 8.26 (m, 1H), 9.62 (d, J=7.4 Hz, 1H), 10.10 (s,1H); MS (ESP+) 389.16 (M+1).

EXAMPLE 903-{[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carbonyl]-amino}-propionicacid methyl ester

HATU (0.202 mmol), diisopropylethylamine (1.008 mmol) and3-amino-propionic acid methyl ester hydrochloride (0.173 mmol) wereadded to a slurry of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid (0.144 mmol; see Example 81 for its preparation) inN,N-dimethylformamide (1.4 mL) at RT. After 15 h, the reaction wasconcentrated in vacuo and purified via reverse phase HPLC(acetonitrile/water gradient with 0.1% TFA) to give 31 mg of a yellowsolid identified as the tri-TFA salt of3-{[3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carbonyl]-amino}-propionicacid methyl ester. ¹H (d6-DMSO, 400 MHz): 2.50 (s, 3H), 2.66 (t, J=6.9Hz, 21), 3.56 (dd, J=12.3, 6.7 Hz, 2H), 3.63 (s, 3H), 6.80 (d, J=5.9 Hz,1H), 7.42 (d, J=7.7 Hz, 1H), 7.52 (dd, J=7.4, 1.8 Hz, 1H), 7.83 (d,J=7.7 Hz, 1H), 7.94 (t, J=7.7 Hz, 1H), 8.22 (d, J=5.9 Hz, 1H), 8.29 (dd,J=1.8, 0.8 Hz, 1H), 8.96 (t, J=5.4 Hz, 1H), 9.62 (d, J=7.4 Hz, 1H); MS(ESP+) 432.06 (M+1).

EXAMPLE 913-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid ([1,4]dioxan-2-ylmethyl)-amide

HATU (0.202 mmol), diisopropylethylamine (0.720 mmol) andC-[1,4]dioxan-2-ylmethylamine (0.173 mmol) were added to a slurry of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid (0.144 mmol; see Example 81 for its preparation) inN,N-dimethylformamide (1.4 mL) at RT. After 15 h, the reaction wasconcentrated in vacuo and purified via reverse phase HPLC(acetonitrile/water gradient with 0.1% TFA) to give 31 mg of a yellowsolid identified as the tri-TFA salt of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid ([1,4]dioxan-2-ylmethyl)-amide. ¹H (d6-DMSO, 400 MHz): 2.50 (s,3H), 3.28 (dd, J=11.3, 9.8 Hz, 1H), 3.35 (q, J=5.7 Hz, 2H), 3.52 (m,2H), 3.65 (m, 1H), 3.71 (m, 1H), 3.78 (m, 2H), 6.81 (d, J=6.0 Hz, 1H),7.42 (d, J=7.7 Hz, 1H), 7.55 (dd, J=7.4, 1.7 Hz, 1H), 7.83 (d, J=7.7 Hz,114), 7.94 (t, J=7.7 Hz, 1H), 8.22 (d, J=6.0 Hz, 1H), 8.32 (m, 1H), 8.96(t, J=5.8 Hz, 1H), 9.62 (d, J=7.4 Hz, 1H); MS (ESP+) 446.55 (M+1).

EXAMPLE 923-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid (2-hydroxy-ethyl)-amide

HATU (0.202 mmol), diisopropylethylamine (0.720 mmol) and ethanolamine(0.173 mmol) were added to a slurry of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid (0.144 mmol; see Example 81 for its preparation) inN,N-dimethylformamide (1.4 mL) at RT. After 17.25 h, the reaction wasconcentrated in vacuo and purified via reverse phase HPLC(acetonitrile/water gradient with 0.1% TFA) to give 39 mg of a yellowsolid identified as the tri-TFA salt of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid (2-hydroxy-ethyl)-amide. ¹H (d6-DMSO, 400 MHz): 2.50 (s, 3H), 3.39(dt, J=6.0, 6.0 Hz, 2H), 3.57 (t, J=6.2 Hz, 2H), 6.78 (d, J=6.0 Hz, 1H),7.41 (d, J=7.8 Hz, 1H), 7.55 (dd, J=7.5, 1.8 Hz, 1H), 7.63, (bs, 2H),7.83 (d, J=7.8 Hz, 1H), 7.93 (d, J=7.8 Hz, 1H), 8.21 (d, J=5.9 Hz, 1H),8.32 (dd, J=1.7, 0.8 Hz, 1H), 8.86 (t, J=5.5 Hz, 1H), 9.61 (d, J=7.4 Hz,1H); MS (ESP+) 390.48 (M+1).

EXAMPLE 933-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid (2-dimethylamino-ethyl)-amide

HATU (0.202 mmol), diisopropylethylamine (0.720 mmol) andN,N-dimethylethylenediamine (0.173 mmol) were added to a slurry of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid (0.144 mmol; see Example 81 for its preparation) inN,N-dimethylformamide (1.4 mL) at RT. After 17.5 h, the reaction wasconcentrated in vacuo and purified via reverse phase HPLC(acetonitrile/water gradient with 0.1% TFA) to give 28 mg of a yellowsolid identified as the tri-TFA salt of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid (2-dimethylamino-ethyl)-amide. ¹H (d6-DMSO, 400 MHz, rotomers):2.49 (s, 3H), 2.88 (s, 3H), 2.89 (s, 3H), 3.32 (t, J=5.8 Hz, 1H), 3.33(t, J=5.8 Hz, 1H), 3.67 (dt, J=5.8 Hz, 1H), 6.80 (d, J=6.0 Hz, If, 7.41(d, J=7.8 Hz, 1H), 7.52 (dd, J=7.3, 1.6 Hz, 1H), 7.82 (d, J=7.8 Hz, 1H),7.98 (t, J=7.8 Hz, 1H), 8.23 (d, J=6.0 Hz, 1H), 8.34 (m, 1H), 9.08 (t,J=5.7 Hz, 1H), 9.46 (bs, 1H), 9.65 (d, J=7.3 Hz, 1H); MS (ESP+) 417.26(M+1).

EXAMPLE 943-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid (2-oxo-2-pyridin-3-yl-ethyl)-amide

HATU (0.202 mmol), diisopropylethylamine (1.008 mmol) and2-amino-1-pyridin-3-yl-ethanone hydrochloride (0.173 mmol) were added toa slurry of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid (0.144 mmol; see Example 81 for its preparation) inN,N-dimethylformamide (1.4 mL) at RT. After 17.75 h, the reaction wasconcentrated in vacuo and purified via reverse phase HPLC(acetonitrile/water gradient with 0.1% TFA) to give 28 mg of a yellowsolid identified as the tri-TFA salt of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid (2-oxo-2-pyridin-3-yl-ethyl)-amide. ¹H (d6-DMSO, 400 MHz): 2.50 (s,3H), 4.91 (d, J=5.3 Hz, 2H), 6.85 (d, J=6.1 Hz, 1H), 7.46 (d, J=7.8 Hz,1H), 7.59 (dd, J=7.4, 1.7 Hz, 1H), 7.65 (dd, J=8.0, 4.9 Hz, 1H), 7.87(m, 1H), 7.96 (m, 1H), 8.24 (d, J=6.1 Hz, 1H), 8.39 (m, 1H), 8.42 (m,if), 8.87 (dd, J=4.9, 1.7 Hz, 1H), 9.26 (m, 1H), 9.40 (t, J=5.8 Hz, 1H),9.68 (d, J=7.4 Hz, 1H); MS (ESP+) 465.13 (M+1).

EXAMPLE 953-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid hydroxyamide

HATU (0.202 mmol), diisopropylethylamine (1.008 mmol) and hydroxylaminehydrochloride (0.173 mmol) were added to a slurry of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid (0.144 mmol; see Example 81 for its preparation) inN,N-dimethylformamide (1.4 mL) at RT. After 22 h, the reaction wasconcentrated in vacuo and purified via reverse phase HPLC(acetonitrile/water gradient with 0.1% TFA) to give 27 mg of a yellowsolid identified as the tri-TFA salt of3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylicacid hydroxyamide. ¹H (d6-DMSO, 400 MHz): 2.69 (s, 3H), 6.81 (d, J=6.0Hz, 1H), 7.43 (d, J=7.8 Hz, 1H), 7.46 (dd, J=7.3, 1.8 Hz, 1H), 7.83 (d,J=7.8 Hz, 1H), 7.94 (t, J=7.8 Hz, 1H), 8.17 (m, 1H), 8.22 (d, J=6.0 Hz,1H), 9.62 (d, J=7.4 Hz, 1H), 11.64 (bs, 1H); MS (ESP+) 362.05 (M+1).

EXAMPLE 962-(6-Methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-ylamine

Hydrogen bromide/acetic acid (30 wt %, 75.0 mmol) and 1.00 Mbromine/acetic acid (32.5 mmol) was added to a solution of1-(6-methyl-pyridin-2-yl)-2-(2-methylsulfanyl-pyrimidin-4-yl)-ethanone(25.0 mmol; see Example 1(b) for its preparation) and catalytic BHT inglacial acetic acid (120 mL) at RT to form a precipitate. After 0.5 hthe reaction was diluted to 400 mL with ether, filtered, washed withether, dried briefly under N₂ gas to give an orange solid. The solid wasadded to a solution of 2,4-diaminopyrimidine (25.0 mmol) anddiisopropylethylamine (100.0 mmol) in ethanol (270 mL) at 85° C. After3.5 h the reaction was allowed to cool to 0° C. and precipitate wasformed. The slurry was filtered, the solid washed with ethanol and airdried to give a solid. This solid was slurried with 2 N aqueous sodiumhydroxide, filtered and washed with water to give 5.059 g of a solididentified as2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-ylamine.¹H NMR (d6-DMSO, 300 MHz): 2.41 (s, 3H), 2.56 (s, 3H), 6.45 (d, J=7.7,1H), 7.24 (s, 2H), 7.25 (d, J=7.8 Hz, 1H), 7.38 (d, J=5.4 Hz, 1H), 7.73(d, J=7.6 Hz, 1H), 7.80 (t, J=7.7 Hz, 1H), 8.45 (d, J=5.4 Hz, 1H), 9.10(d, J=7.6 Hz, 1H); MS (ESP+) 350.4 (M+1).

EXAMPLE 97N-[2-(6-Methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-yl]-3-pyridin-3-yl-propionamide

N,N-Dimethylformamide (0.9 mmol) and thionyl chloride (54.0 mmol) wereadded to a slurry of 3-pyridinepropanoic acid (18.0 mmol) in chloroform(180 mL) at RT. The slurry was heated to 60° C. for 0.5 h, cooled to RTand concentrated in vacuo to yield a solid. This solid was added to aslurry of2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-ylamine(1.14 mmol; see Example 96 for its preparation) in pyridine (40 mL) at0° C. The slurry was warmed to RT. After 23.75 h, the slurry was warmedto 50° C. for a further 2.25 h. The reaction was cooled to RT, dilutedwith water (˜80 mL) and stirred for 0.5 h. The reaction was refrigeratedat 0° C. After 3 d, the reaction was warmed to RT, filtered and washedwith water to yield 398 mg ofN-[2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-yl]-3-pyridin-3-yl-propionamide.¹H NMR (d6-DMSO, 300 MHz): 2.41 (s, 3H), 2.58 (s, 3H), 2.5 (t, J=7.4 Hz,2H), 2.96 (t, J=7.4 Hz, 2H), 7.32 (m, 2H), 7.42 (d, J=5.4 Hz, 1), 7.71(d, J=7.8 Hz, 1H), 7.83 (m, 2H), 8.01 (d, J=7.8 Hz, 1H), 8.42 (dd,J=1.4, 4.8 Hz, 1H), 8.51 (m, 1H), 8.55 (d, J=5.4 Hz, 1H), 9.50 (d, J=7.8Hz, 1H), 11.20 (s, 1H); MS (ESP+) 483.5 (M+1).

EXAMPLE 98N-[3-(2-Methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-3-pyridin-3-yl-propionamide

4.0N Sulfuric acid (0.2 mmol), catalytic sodium tungstate dihydrate, and30 wt % hydrogen peroxide (2.71 mmol) were added to a slurry ofN-[2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-yl]-3-pyridin-3-yl-propionamide(0.82 mmol; see Example 97 for its preparation) in methanol (20 mL) at55° C. After 18.5 h, the reaction was diluted with water (20 mL) andwarmed at 55° C. for an additional 0.75 h. The reaction was then cooledto RT, quenched with saturated sodium thiosulfate, neutralized withsaturated sodium bicarbonate and then cooled to 0° C. for 1.5 h. Thereaction was filtered, washed with 1:1 methanol/water to give 302 mg ofN-[3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-3-pyridin-3-yl-propionamide.¹H NMR (d6-DMSO, 300 MHz): 2.43 (s, 3H), 2.86 (t, J=7.4 Hz, 21), 2.96(t, J=7.4 Hz, 2H), 3.51 (s, 3H), 7.33 (m, 2H), 7.70 (d, J=7.8 Hz, 1H),7.89 (m, 2H), 8.04 (d, J=7.8 Hz, 1H), 8.14 (d, J=5.4 Hz, 1H), 8.41 (m,1H), 8.51 (m, 1H), 8.97 (d, J=5.4 Hz, 1H), 9.56 (d, J=7.8 Hz, 1H), 11.27(s, 1H); MS (ESP+) 515.6 (M+1).

EXAMPLE 99N-[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-3-pyridin-3-yl-propionamide

A solution ofN-[3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-3-pyridin-3-yl-propionamide(0.59 mmol; see Example 98 for its preparation) and ammonium hydroxide(17.70 mmol) in dioxane (10 mL) was warmed to 100° C. for 18 h. Thereaction then concentrated in vacuo and diluted with water to give aprecipitate that was filtered, washed with water and air dried. Theresulting solid was purified via reverse phase HPLC (acetonitrile/watergradient with 0.1% TFA) to give 42 mg of a yellow solid identified asthe tri-TFA salt ofN-[3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-3-pyridin-3-yl-propionamide.¹H NMR (d6-DMSO, 300 MHz): 2.52 (s, 3H), 2.94 (t, J=7.3 Hz, 2H), 3.10(t, J=7.3 Hz, 2H), 6.85 (d, J=6.2 Hz, 1H), 7.43 (d, J=7.8 Hz, 1H), 7.78(m, 2H), 7.93 (t, J=7.8 Hz, 1H), 8.03 (d, J=7.8 Hz, 1H), 8.16 (d, J=6.2Hz, 1H), 8.26 (d, J=7.8 Hz, 1H), 8.68 (d, J=5.4 Hz, 1H), 8.77 (m, 1H),10.08 (d, J=7.8 Hz, 1H), 11.38 (s, 1H); MS (ESP+) 452.19 (M+1).

EXAMPLE 100N-[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-2-(3-methoxy-phenyl)-acetamide

3-Methoxyphenyl acetyl chloride (0.58 mmol) was added to a slurry of2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-ylamine(0.29 mmol; see Example 96 for its preparation) in pyridine (3 mL) at RTand then warmed to 60° C. After 28 h, the reaction was cooled to RT andadditional 2-methoxyphenyl acetyl chloride (1.16 mmol) was added. Thereaction was then warmed to 80° C. for a further 21 hours. The reactionwas cooled to RT, diluted with water (˜10 mL) and stirred for 0.25 h.The reaction then filtered and washed with water to yield 200 mg of animpure solid containing 2-(3-methoxy-phenyl)-N-[2-(6methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-yl]-acetamide.The crude material was used without further purification. MS (ESP+)498.4 (M+1).

EXAMPLE 101N-[3-(2-Methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-2-(3-methoxy-phenyl)-acetamide

4.0N Sulfuric acid (0.1 mmol), catalytic sodium tungstate dihydrate, and30 wt % hydrogen peroxide (1.32 mmol) were added to a slurry of2-(3-methoxy-phenyl)-N-[2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-yl]-acetamide(0.40 mmol) in methanol (10 mL) and heated to 55° C. After 22.5 h, thereaction was diluted with water (10 mL) and warmed at 55° C. for anadditional 1 h. The reaction was then cooled to RT, quenched withsaturated sodium thiosulfate, neutralized with saturated sodiumbicarbonate and then cooled to 0° C. overnight. The reaction warmed toRT, concentrated in vacuo and redissolved in ethyl acetate (25 mL) andwater (10 mL). The organic and aqueous phases were separated and theorganic layer was washed with water (1×10 mL), saturated sodiumbicarbonate (1×10 mL), and brine (1×10 mL), dried (Na₂SO₄), andconcentrated in vacuo to yield 180 mg of an impure solid containingN-[3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-2-(3-methoxy-phenyl)-acetamide.The crude material was used without further purification. MS (ESP+)530.10 (M+1).

EXAMPLE 102N-[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-2-(3-methoxy-phenyl)-acetamide

A solution ofN-[3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-2-(3-methoxy-phenyl)-acetamide(0.34 mmol; see Example 101 for its preparation) and ammonium hydroxide(10.20 mmol) in dioxane (6 mL) was warmed to 100° C. for 18 h. Thereaction concentrated in vacuo, diluted with water and stirred for 4hours at RT. The aqueous layer was extracted with ethyl acetate (2×25mL) The combined organic phases were washed with saturated sodiumbicarbonate (1×20 mL) and brine (1×20 mL), dried (Na₂SO₄), andconcentrated in vacuo. The resulting solid was purified via reversephase HPLC (acetonitrile/water gradient with 0.1% TFA) to give 8 mg of ayellow solid identified as the bis-TFA salt ofN-[3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-2-(3-methoxy-phenyl)-acetamide.¹H NMR (d6-DMSO, 300 MHz): 2.53 (s, 3H), 3.76 (s, 3H), 3.81 (s, 2H),6.83 (d, J=6.2 Hz, 1H), 6.86 (m, 1H), 6.94 (m, 2H), 7.26 (t, J=8.0 Hz,1H), 7.43 (d, J=7.8 Hz, 1H), 7.77 (d, J=7.7 Hz, 1H), 7.93 (t, J=7.8 Hz,1H), 8.04 (d, J=7.7 Hz, 1H), 8.14 (d, J=6.2 Hz, 1H), 10.07 (d, J=7.7 Hz,1H), 11.53 (s, 1H); MS (ESP+) 467.20 (M+1).

EXAMPLE 103N-[2-(6-Methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-yl]-propionamide

Propionyl chloride (1.14 mmol) was added to a slurry of2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-ylamine(0.57 mmol; see Example 96 for its preparation) in pyridine (5.7 mL) atRT and the slurry was warmed to 50° C. After 19 h, the reaction wascooled to RT and additional propionyl chloride (1.14 mmol) was added.The reaction was warmed to 50° C. for a further 5 h. The reaction wascooled to RT, diluted with water (˜15 mL) and refrigerated at 0° C.After 4 d, the reaction was warmed to RT, filtered and washed with waterto yield 208 mg ofN-[2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-yl]-propionamide.¹H NMR (d6-DMSO, 300 MHz): 1.10 (t, 3H), 2.42 (s, 3H), 2.50 (q, 2H),2.58 (s, 3H), 7.31 (dd, J=2.1, 6.5 Hz, 1H), 7.43 (d, J=5.4 Hz, 1H), 7.84(m, 2H), 8.03 (d, J=7.7 Hz, 1H), 8.55 (d, J=5.4 Hz, 1H), 9.50 (d, J=7.7Hz, 1H), 11.11 (s, 1H); MS (ESP+) 406.25 (M+1).

EXAMPLE 104N-[3-(2-Methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-propionamide

4.0N Sulfuric acid (0.1 mmol), catalytic sodium tungstate dihydrate, and30 wt % hydrogen peroxide (1.69 mmol) were added to a slurry ofN-[2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-yl]-propionamide(0.51 mmol; see Example 103 for its preparation) in methanol (13 mL) andheated to 55° C. After 19.5 h, the reaction was diluted with water (13mL) and warmed at 55° C. for an additional 1 h. The reaction was thencooled to RT, quenched with saturated sodium thiosulfate, neutralizedwith saturated sodium bicarbonate and then cooled to 0° C. for 2 h. Thereaction was filtered, washed with water to give 176 mg ofN-[3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-propionamide.¹H NMR (d6-DMSO, 300 MHz): 1.10 (t, J=7.5 Hz, 1H), 2.43 (s, 3H), 2.50(q, 2H), 3.50 (s, 3H), 7.35 (dd, J=1.9, 6.7 Hz, 1H), 7.89 (m, 2H), 8.06(d, J=7.8 Hz, 1H), 8.14 (d, J=5.4 Hz, 1H), 8.97 (d, J=5.4 Hz, 1H), 9.56(d, J=7.8 Hz, 1H), 11.19 (s, M1); MS (ESP+) 438.4 (M+1).

EXAMPLE 105N-[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-propionamide

A solution ofN-[3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-propionamide(0.39 mmol; see Example 104 for its preparation) and ammonium hydroxide(11.73 mmol) in dioxane (9 mL) was warmed to 100° C. for 6 h. Thereaction then concentrated in vacuo and the resulting solid was purifiedvia reverse phase HPLC (acetonitrile/water gradient with 0.1% TFA) togive 120 mg of a yellow solid identified as the bis-TFA salt ofN-[3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-propionamide.¹H NMR (d6-DMSO, 300 MHz): 1.10 (t, J=7.5 Hz, 3H), 2.50 (q, 2H), 2.53(s, 3H), 6.85 (d, J=6.2 Hz, 1H), 7.44 (d, J=7.8 Hz, 1H), 7.77 (d, J=7.8Hz, 1H), 7.87 (bs, 2H), 7.94 (t, J=7.8 Hz, 1H), 8.10 (d, J=7.8 Hz, 1H),8.15 (d, J=6.2 Hz, M1), 10.09 (d, J=7.8 Hz, 1H), 11.28 (s, 1H); MS(ESP+) 375.2 (M+1).

EXAMPLE 1063,3-Dimethyl-N-[2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-yl]-butyramide

Tert-butylacetyl chloride (0.58 mmol) was added to a slurry of2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-ylamine(0.57 mmol; see Example 96 for its preparation) in pyridine (3 mL) atRT. After 25 h, additional tert-butylacetyl chloride (0.58 mmol) wasadded and the reaction was stirred for a further 17 h. The reactiondiluted with ethyl acetate (20 mL) and water (10 mL). The organic andaqueous phases were separated and the organic layer was washed withwater (1×10 mL) and brine (1×10 mL), dried (Na₂SO₄), and concentrated invacuo to yield 173 mg of3,3-dimethyl-N-[2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-yl]-butyramide.¹H NMR (d6-DMSO, 300 MHz): 0.98 (s, 9H), 2.08 (s, 2H), 2.42 (s, 3H),2.59 (s, 3H), 7.31 (dd, J=1.6, 6.6 Hz, 1H), 7.43 (d, J=5.4 Hz, 1H), 7.82(m, 21), 8.06 (d, J=7.8 Hz, 1H), 8.55 (d, J=5.4 Hz, 1H), 9.51 (d, J=7.8Hz, 1H), 11.06 (s, 1H); MS (ESP+) 448.5 (M+1).

EXAMPLE 107N-[3-(2-Methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-3,3-dimethyl-butyramide

4.0 N Sulfuric acid (0.1 mmol), catalytic sodium tungstate dihydrate,and 30 wt % hydrogen peroxide (1.25 mmol) were added to a slurry3,3-dimethyl-N-[2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-yl]-butyramide(0.38 mmol; see Example 106 for its preparation) in methanol (10 mL) at55° C. After 20.5 h, the reaction was diluted with water (10 mL) andwarmed at 55° C. for an additional 0.75 h. The reaction was then cooledto RT, quenched with saturated sodium thiosulfate, quenched withsaturated sodium bicarbonate and then cooled to 0° C. for 1.5 h. Thereaction was filtered, washed with 1:1 methano/water to give 82 mg ofN-[3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-3,3-dimethyl-butyramide.¹H NMR (d6-DMSO, 300 MHz): 1.05 (s, 9H). 2.39 (s, 2H), 2.44 (s, 3H),3.51 (s, 3H), 7.35 (dd, J=2.1, 6.5 Hz, 1H), 7.89 (m, 2H), 8.10 (d, J=7.8Hz, 1H), 8.15 (d, J=5.4 Hz, 1H), 8.97 (d, J=5.4 Hz, 1H), 9.57 (d, J=7.8Hz, 1H), 11.13 (s, 1H); MS (ESP+) 480.5 (M+1).

EXAMPLE 108N-[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-3,3-dimethyl-butyramide

A solution ofN-[3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-3,3-dimethyl-butyramide(0.17 mmol; see Example 107 for its preparation) and ammonium hydroxide(5.10 mmol) in dioxane (4 mL) was warmed to 100° C. for 19 h. Thereaction concentrated in vacuo, diluted with water and stirred for 2hours at RT. The resulting solid was filtered, washed with water, andpurified via reverse phase HPLC (acetonitrile/water gradient with 0.1%TFA) to give 8 mg of a yellow solid identified as the bis-TFA salt ofN-[3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-3,3-dimethyl-butyramide.¹H NMR (d6-DMSO, 300 MHz): 1.05 (s, 9H), 2.39 (s, 2H), 2.53 (s, 3H),6.85 (d, J=6.2 Hz, 1H), 7.43 (d, J=7.8 Hz, 1H), 7.67 (bs, 2H), 7.77 (d,J=7.8 Hz, 1H), 7.93 (t, J=7.8 Hz, 1H), 8.10 (d, J=7.8 Hz, 1H), 8.15 (d,J=6.2 Hz, 1H), 10.05 (d, J=7.8 Hz, 1H), 11.20 (s, 1H); MS (ESP+) 417.26(M+1); MS (ESP−) 415.28 (M−1).

EXAMPLE 109N-[2-(6-Methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-yl]-nicotinamide

Nicotinoyl chloride hydrochloride (0.58 mmol) was added to a slurry of2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-ylamine(0.29 mmol; see Example 96 for its preparation) in pyridine (3 mL) atRT. After 24 h, the reaction was diluted with water (10 mL), filteredand washed with water to yield 100 mg ofN-[2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-yl]-nicotinamide.¹H NMR (d6-DMSO, 300 MHz): 2.43 (s, 3H), 2.60 (s, 3H), 7.32 (m, 1H),7.47 (d, J=5.3 Hz, 1H), 7.61 (dd, J=4.8, 8.0 Hz, 1H), 7.85 (m, 2H), 8.13(d, J=7.7 Hz, 1H), 8.40 (dt, J=1.9, 8.0 Hz, 1H), 8.58 (d, J=5.3, 1H),8.80 (dd, J=1.5, 4.8 Hz, 1H), 9.19 (m, 1H), 9.59 (d, J=7.7 Hz, 1H),11.79 (s, 1H); MS (ESP+) 455.4 (M+1).

EXAMPLE 110N-[3-(2-Methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-nicotinamide

8289-042

4.0 N Sulfuric acid (0.04 mmol), catalytic sodium tungstate dihydrate,and 30 wt % hydrogen peroxide (0.63 mmol) were added to a slurry ofN-[2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-yl]-nicotinamide(0.19 mmol; see Example 109 for its preparation) in methanol (5 mL) andwarmed to 55° C. After 20.5 h, the reaction was diluted with water (5mL) and warmed at 55° C. for an additional 0.75 h. The reaction was thencooled to RT, quenched with saturated sodium thiosulfate, neutralizedwith saturated sodium bicarbonate and then cooled to 0° C. for 1.5 h.The reaction was filtered, washed with 1:1 methanol/water to give 66 mgN-[3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-nicotinamide.¹H NMR (d6-DMSO, 300 MHz): 2.44 (s, 3H), 3.53 (s, 3H), 7.36 (d, J=6.9Hz, 1H), 7.60 (dd, J=4.7, 7.8 H z, 1H), 7.91 (m, 2H), 8.17 (m, 2H), 8.41(d, J=7.8 Hz, 1H), 8.81 (d, J=4.6 Hz, 1H), 9.00 (d, J=5.3 Hz, 1H), 9.19(m, 1H), 9.64 (d, J=7.8 Hz, 1H), 11.85 (s, 1H); MS (ESP+) 487.3 (M+1).

EXAMPLE 111N-[3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-nicotinamide

A solution ofN-[3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-nicotinamide(0.14 mmol; see Example 110 for its preparation) and ammonium hydroxide(4.20 mmol) in dioxane (3 mL) was warmed to 100° C. for 19 h. Thereaction concentrated in vacuo, diluted with water and stirred for 2hours at RT. The resulting solid was filtered, washed with water, andpurified via reverse phase HPLC (acetonitrile/water gradient with 0.1%TFA) to give 8 mg of a yellow solid identified as the tri-TFA salt ofN-[3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-nicotinamide.¹H NMR (d₆-DMSO, 300 MHz): 2.53 (s, 3H), 6.88 (d, J=6.2 Hz, 1H), 7.43(d, J=7.8 Hz, 1H), 7.61 (dd, J=4.9, 8.0 Hz, 1H), 7.80 (d, J=7.9 Hz, 1H),7.94 (t, J=7.8 Hz, 1H), 8.16 (m, 2H), 8.42 (dt, J=2.0, 7.9 Hz, 1H), 8.82(dd, J=1.7, 4.9 Hz, 1H), 9.20 (m, 1H), 10.15 (d, J=7.8 Hz, 1H), 11.90(s, 1H); MS (ESP+) 424.27 (M+1); MS (ESP−) 422.28 (M−1).

EXAMPLE 1122-(6-Methyl-pyridin-2-yl)-3-pyrimidin-4-yl-imidazo[1,2-a]pyrimidin-7-ylamine

To a 100 mL flask was added2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-ylamine(see Example 96 for its preparation), ethanol (18 mL) and ammoniumhydroxide (15% aq., 16 mL). In another 100 mL flask, Raney nickel(slurry in water, ˜1.5 g) was washed several times, alternating betweenwater and ethanol until the washes were no longer cloudy. After removingthe last wash, the Raney nickel was transferred to the reaction flaskusing ethanol (˜18 mL) and the reaction was warmed to 78° C. After 21.5h, the reaction was cooled to RT, filtered through Celite and rinsedwith ethanol. The filtrate was concentrated in vacuo. The resultingmaterial was purified via reverse phase HPLC (acetonitrile/watergradient with 0.1% TFA) to give 104 mg of a yellow solid identified asthe TFA salt of2-(6-methyl-pyridin-2-yl)-3-pyrimidin-4-yl-imidazo[1,2-a]pyrimidin-7-ylamine.¹H NMR (d₆-DMSO, 300 MHz): 2.47 (s, 3H), 6.71 (d, J=7.7 Hz, 1H), 7.43(d, J=7.6 Hz, 1H), 7.64 (d, J=7.8 Hz, M1), 7.68 (dd, J=1.1, 5.4 Hz, 1H),7.89 (t, J=7.8 Hz, 1H), 8.84 (d, J=5.4 Hz, 1H), 9.08 (d, J=7.6 Hz, 1H),9.35 (d, J=1.1 Hz, 1H); MS (ESP+) 304.22 (M+1).

Examples of compounds of the present invention are also described in thefollowing table (Table I) TABLE I Name 1H NMR MS m/z[3-(2-amino-pyrimidin-4-yl)- 333.3 2-(6-methyl-pyridin-2-yl)- (M+1)imidazo[1,2-a]pyridin-7-yl]- methanol [3-(4-Methyl-piperidin-1-yl)-(d6-DMSO, 400MHz): 0.95(m, 442.4 propyl]-{4-[2-(6-methyl- 3H), 1.35(m,2H), 1.62(m, (M+1) pyridin-2-yl)-imidazo[1,2- 1H), 1.81(m, 2H), 2.00(m,2H), a]pyridin-3-yl]-pyrimidin- 2.51(s, 3H), 2.93(m, 2H), 2-yl}-amine3.17(m, 2H), 3.47(m, 4H), 6.76(bs, 1H), 7.20(t, 1H, J=7.0Hz), 7.39(d,1H, J=7.0Hz), 7.62(m, 2H), 7.82(m, 2H), 7.91(t, 1H, J=7.0Hz), 8.31(d,1H, J=4.7Hz), 9.17(bs, 1H) [4-(2-Pyridin-2-yl-imidazo[1, 380.22-a]pyridin-3-yl)-pyrimidin- (M+1) 2-yl]-pyridin-3-ylmethyl- amine{4-[2-(6-methyl-pyridin-2- 343.2 yl)-imidazo[1,2-a]-pyridin-3- (M+1)yl]-pyrimidin-2-yl}-(1H- tetrazol-5-yl)-amine {4-[2-(6-Methyl-pyridin-2-(d6-DMSO, 400MHz): 1.38(m,  428.25 yl)-imidazo[1,2-a]-pyridin- 1H),1.66(m, 3H), 1.80(m, 2H), (M+1) 3-yl]-pyrimidin-2-yl}-(3- 2.49(s, 3H),2.87(m, 2H), piperidin-1-yl-propyl)-amine 3.13(m, 2H), 3.42(m, 4H),6.72(bs, 1H), 7.17(t, 1H, J=7.3Hz), 7.37(d, 1H, J=7.3Hz), 7.58(t, 1H,J=7.3Hz), 7.65(bs, 1H), 7.83(m, 3H), 8.28(d, 1H, J=5.3Hz), 9.32(bs, 1H){7,7-Dimethyl-8-[5-(4-{4-[2- 859.1 (6-methyl-pyridin-2-yl)- (M+1)imidazo[1,2-a]pyridin-3-yl]- pyrimidin-2-ylamino}-butyl-carbamoyl)-pentyl]-2-oxo-4- trifluoromethyl-7,8-dihydro-2H-1-oxa-8-aza-anthracen-5- yl}-methanesulfonic acid2-(2,7-Difluoro-6-hydroxy-3- 868.4 oxo-9,9a-dihydro-3H-xanthen- (M+1)9-yl)-3,5,6-trifluoro-4-[(4-{4- [2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]- pyrimidin-2-ylamino}-butyl-carbamoyl)-methylsulfanyl]- benzoic acid 2-(6-Methyl-pyridin-2-yl)-3-pyrimidin-4-yl-imidazo[1,2- a]pyridine 3-(2-amino-pyrimidin-4-yl)-2-(DMSO-d6, 400MHz)2.93(s,  318.21 (6-methyl-pyridin-2-yl)- 3H), 6.63(d,J=7.48Hz, 1H), (M+1) imidazo[1,2-a]pyridin-8- 6.66(d, J=7.72Hz, 1H),7.89(dd, ylamine J=7.77, 7.75Hz, 1H), 8.10(d, J=6.12Hz, 1H), 8.89(d,J=5.70Hz, 1H) 3-(2-amino-pyrimidin-4-yl)-2- (DMSO-d6, 400MHz)2.42(s,328.2 (6-methyl-pyridin-2-yl)- 3H), 6.74(d, J=5.76Hz, 1H), (M+1)imidazo[1,2-a]pyridine-6- 7.34(d, J=7.61Hz, 1H), 7.50(br carbonitrile s,2H), 7.74-7.77(m, 2H), 7.85(dd, J=7.75, 7.71Hz, 1H), 7.91(d, J=9.28Hz,1H), 8.17(d, J=5.75Hz, 1H), 10.08(s, 1H) 3-(2-Amino-pyrimidin-4-yl)- 486.24 2-(6-methyl-pyridin-2-yl)- (M+1) imidazo[1,2-a]pyridine-6-carboxylic acid [3-(4-ethyl- piperazin-1-yl)-propyl]-amide3-(2-amino-pyrimidin-4-yl)-2- (DMSO-d6, 400MHz)2.45(s,  346.22(6-methyl-pyridin-2-yl)- 3H), 6.81(d, J=5.69Hz, 1H), (M+1)imidazo[1,2-a]pyridine-6- 7.34(d, J=7.49Hz, 1H), 7.44(br carboxylic acidamide s, 2H), 7.64(br s, 1H), 7.78-7.82(m, 2H), 7.84-7.89(m, 2H),8.12(br s, 1H), 8.23(d, J=5.69Hz, 1H), 9.63(s, 1H)3-(2-Amino-pyrimidin-4-yl)-  362.14 2-(6-methyl-pyridin-2-yl)- (M+1)imidazo[1,2-a]pyridine-6- carboxylic acid hydroxyamide3-(2-methanesulfonyl- (DMSO-d6, 400MHz)2.34(s,  391.18pyrimidin-4-yl)-2-(6-methyl- 3H), 3.46(s, 3H), 7.30(d, (M+1)pyridin-2-yl)-imidazo[1,2- J=7.61Hz, 1H), 7.78(dd,a]pyridine-6-carbonitrile J=9.33Hz, 1.51Hz, 1H), 7.84(dd, J=7.71,7.75Hz, 1H), 7.94(d, J=7.25Hz, 1H), 7.94(d, J=9.61Hz, 1H), 8.16(d,J=5.35Hz, 1H), 9.04(d, J=5.35Hz, 1H), 9.80(s, 1H) 3-(2-Methylsulfanyl-320.2 pyrimidin-4-yl)-2-pyridin-2- (M+1) yl-imidazo[1,2-a]pyridine3,6-Dichloro-N-(4-{4-[2-(6- 939.5 methyl-pyridin-2-yl)- (M+1)imidazo[1,2-a]pyridin-3-yl]- pyrimidin-2-ylamino}-butyl)-2-(2,4,5,7-tetrachloro-6- hydroxy-3-oxo-9,9a-dihydro-3H-xanthen-9-yl)-terephthala- mic acid 4-(2-Pyridin-2-yl-imidazo[1,289.2 2-a]pyridin-3-yl)-pyrimidin-2- (M+1) ylamine4-[2-(6-Chloro-pyridin-2-yl)- 323.1 imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine 4-[2-(6-Methyl-pyridin-2-yl)- 371.27-trifluoromethyl-imidazo[1, (M+1) 2-a]pyridin-3-yl]-pyrimidin-2-ylamine 4-[2-(6-methyl-pyridin-2-yl)- 313.2 imidazo[1,2-a]pyridin-3-yl]-(M+1) pyrimidine-2-carbonitrile 4-[2-(6-methyl-pyridin-2-yl)- 331.2imidazo[1,2-a]pyridin-3-yl]- (M+1) pyrimidine-2-carboxylic acid amide4-[6-Bromo-2-(6-methyl- (400MHz, CDCl₃)(J=Hz) 381.1pyridin-2-yl)-imidazo[1,2- δ 9.64(s; 1H), 8.15(d; 1H; &a]pyridin-3-yl]-pyrimidin-2- J=6.0), 7.88(t; 1H; J=8.0); 383.1 ylamine7.76(d; 1H; J=9.4), 7.70(dd; (M+1) 1H; J=9.7, 2.1), 7.36(d; 1H; J=7.7),6.77(d; 1H; J=6.3), 2.43(s; 3H) 4-[6-Fluoro-2-(6-methyl- (400MHz,CDCl₃)(J=Hz) 321.2 pyridin-2-yl)-imidazo[1,2- δ 9.80(dd; 1H; J=3.6,2.0), (M+1) a]pyridin-3-yl]-pyrimidin-2- 8.11(d; 1H; J=6.3), 7.88(m;2H); ylamine 7.73(d; 1H; J=7.7), 7.69(dt; 1H; J=7.9, 2.6), 7.37(d; 1H;J=8.0), 6.75(d; 1H; J=6.2), 2.45(s, 3H). 4-[6-methyl-2-(6-methyl-(DMSO-d6, 400MHz)2.39(s, 317.2 pyridin-2-yl)-imidazo[1,2- 3H), 2.49(s,3H), 6.73(d, (M+1) a]pyridin-3-yl]-pyrimidin- J=5.99Hz, 1H), 7.40(d,2-ylamine J=7.69Hz, 1H), 7.55(dd, J=9.11, 1.17Hz, 1H), 7.72(d, J=7.76,1H), 7.76(d, J=9.12Hz, 1H), 7.89(dd, J=7.77, 7.77Hz, 1H), 8.17(d,J=5.99Hz, 1H), 9.37(s, 1H) 4-[7-aminomethyl-2-(6- 332.2methyl-pyridin-2-yl)- (M+1) imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine 4-[8-Benzyloxy-2-(6-methyl- 410.1pyridin-2-yl)-imidazo[1,2- (M+1) a]pyridin-3-yl]-pyrimidin-2-ol4-[8-Benzyloxy-2-(6-methyl- (CDC₃, 400MHz)9.03(d, 440.1pyridin-2-yl)-imidazo[1,2- J=6.77Hz, 1H), 8.34(d, (M+1)a]pyridin-3-yl]-pyrimidin-2- J=5.38Hz, 1H), 7.84(d, ylamine J=7.73Hz,1H), 7.68(dd, J=7.73, 7.70Hz, 1H), 7.49(d, J=7.16Hz, 2H), 7.36(dd,J=7.57, 6.99Hz, 2H), 7.31(d, J=7.19Hz, 1H), 7.16(d, J=5.43Hz, 2H),6.74(dd, J=7.44, 7.20Hz, 1H), 5.41(s, 3H), 2.60(s, 3H), 2.50(s, 3H)5-Dimethylamino- 607.1 naphthalene-1-sulfonic acid (M+1)(4-{4-[2-(6-methyl-pyridin- 2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}- butyl)-amide 6-(2,7-Difluoro-6-hydroxy-768.1 3-oxo-3H-xanthen-9-yl)-N- (M+1) (4-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin- 3-yl]-pyrimidin-2-ylamino}-butyl)-isothalamic acid 6-Amino-9-[2-carboxy-5- 730.2(4-{4-[2-(6-methyl-pyridin- (M+1) 2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}- butylcarbamoyl)-phenyl]-xanthen-3-ylidene-ammonium 6-Bromo-2-(6-methyl-pyridin- (300MHz,CDCl₃)(J=Hz)δ 412.1 2-yl)-3-(2-methylsulfanyl- 9.73(s; 1H), 8.29(d; 1H;J=5.4), & pyrimidin-4-yl)-imidazo[1,2- 7.62(m; 2H); 7.55(d; 1H; 414.0a]pyridine J=9.0); 7.36(dd; 1H; J=9.3, (M+1) 1.8), 7.12(m; 2H), 2.60(s;3H), 2.48(s; 3H) 6-Fluoro-2-(6-methyl-pyridin- (300MHz, CDCl₃)(J=Hz)δ352.1 2-yl)-3-(2-methylsulfanyl- 9.92(s; 1H), 8.38(d; 1H; J=5.1), (M+1)pyrimidin-4-yl)-imidazo[1,2- 7.76(m; 3H); 7.33(m; 3H); a]pyridine2.67(s; 3H), 2.57(s; 3H). 7-Amino-4-methyl-3-[(4-{4- 669.1[2-(6-methyl-pyridin-2-yl)- (M+1) imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}- butylcarbamoyl)-methyl]-2-oxo-2H-chromene-6-sulfonic acid Cyclobutyl-{4-[2-(6- (d6-DMSO, 400MHz):1.72(m, 329.3 methyl-pyridin-2-yl)- 2H), 2.07(m, 2H), 2.29(m, 2H), (M+1)imidazo[1,2-a]pyridin-3- 2.55(s, 3H), 4.36(m, 1H),yl]-pyrimidin-2-yl}-amine 6.72(d, 1H, J=3.5Hz, 7.30(t, 1H, J=7.0Hz),7.47(d, J=7.0Hz), 7.70(t, 1H, J=7.0Hz), 7.78(d, 1H, J=8.2Hz), 7.88(d,1H, J=9.4Hz), 7.97(t, 1H, J=9.4Hz), 8.15(bs, 1H), 8.28(d, 1H, J=4.7Hz),9.41(bs, 1H) Cyclopropyl-methyl-{4-[2-(6- (d6-DMSO, 400MHz): 0.78(m,351.3 methyl-pyridin-2-yl)- 2H), 0.89(m, 2H), 2.51(s, 3H), (M+1)imidazo[1,2-a]pyridin-3-yl]- 2.88(m, 1H), 3.18(s, 3H),pyrimidin-2-yl}-amine 6.81(d, 1H, J=5.7Hz), 7.26(t, 1H, J=7.0Hz),7.44(d, 1H, J=7.5Hz), 7.65(m, 1H), 7.77(d, 1H, J=7.8Hz), 7.85(d, 1H,J=8.8Hz), 7.93(t, 1H, J=7.5Hz), 8.37(d, 1H, J=5.7Hz), 9.60(d, 1H,J=7.5Hz) Isopropyl-{4-[2-(6-methyl- (d6-DMSO, 400MHz): 1.23(d, 345.7pyridin-2-yl)-imidazo[1,2-a]- 6H, J=6.8Hz), 2.55(s, 3H), (M+1)pyridin-3-yl]-pyrimidin-2-yl}- 4.10(bs, 1H), 6.70(bs, 1H), amine 7.28(t,1H, J=6.8Hz), 7.46(d, 1H, J=6.8Hz), 7.67(t, 1H, J=8.1Hz), 7.78(d, 1H,J=8.1Hz), 7.86(d, 1H, J=8.1Hz), 7.97(t, 1H, J=9.6Hz), 8.26(d, 1H,J=6.8Hz), 9.48(bs, 1H) N-(4-{4-[2-(6-Methyl- pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2- ylamino}-butyl)- (BODIPY-FL)amideN-(4-{4-[2-(6-Methyl- 1075.1  pyridin-2-yl)imidazo[1,2- (M+1)a]pyridin-3-yl]-pyrimidin- 2-ylamino}-butyl)- (Texan Red-X) amideN-[3-(2-amino-pyrimidin-4- 361.3 yl)-2-(6-methyl-pyridin- (M+1)2-yl)-imidazo[1,2- a]pyrimidin-7-yl]-acetamideN-{4-[2-(6-methyl-pyridin-2- (DMSO-d6, 400MHz)2.14(s, 345.0yl)-imidazo[1,2-a]pyridin-3- 3H), 2.44(s, 3H), 7.12(dd, (M+1)yl]-pyrimidin-2-yl}-acetamide J=6.99, 6.92Hz, 1H), 7.18(d, 5.46Hz, 1H),7.36(d, J=7.66Hz, 1H), 7.54(dd, J=8.09, 7.24Hz, 1H), 7.75(d, J=6.15Hz,1H), 7.76(d, J=7.33Hz, 1H), 7.89(dd, J=7.75, 7.69Hz, 1H)Cell-Free Assay for Evaluating Inhibition of Activin Type I ReceptorKinase Activity

The TGFβ or activin inhibitory activity of compounds of formula (I) canbe assessed by methods described in the following examples.

EXAMPLE 113

Cell-Free Assay for Evaluating Inhibition of Autophosphorylation of TGFβType I Receptor

The serine-threonine kinase activity of TGFβ type I receptor wasmeasured as the autophosphorylation activity of the cytoplasmic domainof the receptor containing an N-terminal poly histidine, TEV cleavagesite-tag, e.g., His-TGFβRI. The His-tagged receptor cytoplasmic kinasedomains were purified from infected insect cell cultures using theGibco-BRL FastBac HTb baculovirus expression system.

To a 96-well Nickel FlashPlate (NEN Life Science, Perkin Elmer) wasadded 20 μl of 1.25 μCi ³³P-ATP/25 μM ATP in assay buffer (50 mM Hepes,60 mM NaCl, 1 mM MgCl₂, 2 mM DTT, 5 nM MnCl₂, 2% glycerol, and 0.015%Brij 35). 10 μl of test compounds of formula (I) prepared in 5% DMSOsolution were added to the FlashPlate. The assay was then initated withthe addition of 20 ul of assay buffer containing 12.5 pmol of His-TGFβRIto each well. Plates were incubated for 30 minutes at room temperatureand the reactions were then terminated by a single rinse with TBS.Radiation from each well of the plates was read on a TopCount (Packard).Total binding (no inhibition) was defined as counts measured in thepresence of DMSO solution containing with no test compound andnon-specific binding was defined as counts measured in the presence ofEDTA or no-kinase control.

Alternatively, the reaction performed using the above reagents andincubation conditions but in a microcentrifuge tube was analyzed byseparation on a 4-20% SDS-PAGE gel and the incorporation of radiolabelinto the 40 kDa His-TGF□RI SDS-PAGE band was quantitated on a StormPhosphoimager (Molecular Dynamics).

Compounds of formula (I) typically exhibited IC₅₀ values of less than 10μM; some exhibited IC₅₀ values of less than 0.1 μM.

EXAMPLE 114

Inhibition of the Activin type I receptor (Alk 4) kinaseautophosphorylation activity by test compounds of formula (I) can bedetermined in a similar manner as described above in Example 7 exceptthat a similarly His-tagged form of Alk 4 (His-Alk 4) was used in placeof the His-TGFβRI.

EXAMPLE 115

Assay for Evaluating Cellular Inhibition of TGFβ Signaling andCytotoxicity

Biological activity of compounds of formula (I) were determined bymeasuring their ability to inhibit TGFβ-induced PAI-Luciferase reporteractivity in HepG2 cells.

HepG2 cells were stably transfected with the PAI-luciferase reportergrown in DMEM medium containing 10% FBS, penicillin (100 U/ml),streptomycin (100 μg/ml), L-glutamine (2 mM), sodium pyruvate (1 mM),and non essential amino acids (1×). The transfected cells were thenplated at a concentration of 2.5×10⁴ cells/well in 96 well plates andstarved for 3-6 hours in media with 0.5% FBS at 37° C. in a 5% CO₂incubator. The cells were then stimulated with ligand either 2.5 ng/mlTGFβ in the starvation media containing 1% DMSO and the presence orabsence of test compounds of of formula (I) and incubated as describedabove for 24 hours. The media was washed out in the following day andthe luciferase reporter activity was detected using the LucLiteLuciferase Reporter Gene Assay kit (Packard, cat. no. 6016911) asrecommended. The plates were read on a Wallac Microbeta plate reader,the reading of which was used to determine the IC₅₀ values of compoundsof formula (I) for inhibiting TGFβ-induced PAI-Luciferase reporteractivity in HepG2 cells. Compounds of formula (I) typically exhibitedIC₅₀ values of less 10 uM.

Cytotoxicity was determined using the same cell culture conditions asdescribed above. Specifically, cell viability was determined afterovernight incubation with the CytoLite cell viability kit (Packard, cat.no. 6016901). Compounds of formula (I) typically exhibited LD₂₅ valuesgreater than 10 μM.

EXAMPLE 116

Assay for Evaluating Cellular Inhibition of TGFβ Signaling

The cellular inhibition of activin signaling activity by test compoundsof formula (I) were determined in a similar manner as described above inExample 115 except that 100 ng/ml of activin is added to serum starvedcells in place of the 2.5 ng/ml TGFβ.

EXAMPLE 117

Assay for TGFβ-Induced Collagen Expression

Preparation of Immortalized Collagen Promotor-Green Fluorescent ProteinCells

Fibroblasts were derived from the skin of adult transgenic miceexpressing Green Fluorescent Protein (GFP) under the control of thecollagen 1A1 promoter (see Krempen, K. et al., Gene Exp. 8: 151-163(1999)). Cells were immortalised with a temperature sensitive large Tantigen that is active at 33° C. Cells are expanded at 33° C. thentransferred to 37° C. so that the large T becomes inactive (see Xu, S.et al., Exp. Cell Res. 220: 407-414 (1995)). Over the course of about 4days and one split, the cells cease proliferating. Cells are then frozenin aliquots sufficient for a single 96 well plate.

Assay of TGFβ-Induced Collagen-GFP Expression

Cells are thawed, plated in complete DMEM (contains nonessential aminoacids, 1 mM sodium pyruvate and 2 mM L-glutamine) with 10% fetal calfserum and incubated overnight at 37° C., 5% CO₂. The following day, thecells are trypsinized and transferred into 96 well format with 30,000cells per well in 50 μl complete DMEM containing 2% fetal calf serum,but without phenol red. The cells are incubated at 37° C. for 3 to 4hours to allow them to adhere to the plate, solutions containing testcompounds of formula (I) are then added to triplicate wells with noTGFβ, as well as triplicate wells with 1 ng/ml TGFβ. DMSO was also addedto all of the wells at a final concentration of 0.1%. GFP fluorescenceemission at 530 nm following excitation at 485 nm was measured at 48hours after the addition of solution containing test compounds on aCytoFluor microplate reader (PerSeptive Biosystems). The data are thenexpressed as the ratio of TGFβ-induced to non-induced for each testsample.

OTHER EMBODIMENTS

It is to be understood that while the invention has been described inconjunction with the detailed description thereof, the foregoingdescription is intended to illustrate and not limit the scope of theinvention, which is defined by the scope of the appended claims. Otheraspects, advantages, and modifications are within the scope of thefollowing claims.

1. A compound of the following formula:

wherein each of X₁, X₂, X₃, and X₄ is independently selected from CR^(x) or N; provided that only two of X₁, X₂, X₃, and X₄ can be N simultaneously; each of Y₁ and Y₂ is independently selected from CR^(y) or N; provided that at least one of Y₁ and Y₂ must be N; each R¹ is independently selected from alkyl, alkenyl, alkynyl, alkoxy, acyl, halo, hydroxy, amino, nitro, cyano, guanadino, amidino, carboxy, sulfo, mercapto, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, aminocarbonyl, alkylcarbonylamino, alkylsulfonylamino, alkoxycarbonyl, alkylcarbonyloxy, urea, thiourea, sulfamoyl, sulfamide, carbamoyl, cycloalkyl, cycloalkyloxy, cycloalkylsulfanyl, heterocycloalkyl, heterocycloalkyloxy, heterocycloalkylsulfanyl, aryl, aryloxy, arylsulfanyl, aroyl, heteroaryl, heteroaryloxy, heteroarylsulfanyl, or heteroaroyl; each R² is independently selected from alkyl, alkenyl, alkynyl, acyl, halo, hydroxy, —NH₂, —NH(alkyl), —N(alkyl)₂, —NH(cycloalkyl), —N(alkyl)(cyclocalkyl), —NH(heterocycloalkyl), —NH(heteroaryl), —NH-alkyl-heterocycloalkyl, —NH-alkyl-heteroaryl, —NH(aralkyl), cycloalkyl, (cycloalkyl)alkyl, aryl, aralkyl, aroyl, heterocycloalkyl, (heterocycloalkyl)alkyl, heteroaryl, heteroaralkyl, heteroaroyl, nitro, cyano, guanadino, amidino, carboxy, sulfo, mercapto, alkoxy, cycloalkyloxy, (cycloalkyl)alkoxy, aryloxy, arylalkoxy, heterocycloalkyloxy, (heterocycloalkyl)alkoxy, heteroaryloxy, heteroarylalkoxy, alkylsulfanyl, cycloalkylsulfanyl, (cycloalkyl)alkylsulfanyl, arylsulfanyl, aralkylsulfanyl, heterocycloalkylsulfanyl, (heterocycloalkyl)alkylsulfanyl, heteroarylsulfanyl, heteroarylalkylsulfanyl, alkylsulfinyl, alkylsulfonyl, aminocarbonyl, aminosulfonyl, alkylcarbonylamino, cycloalkylcarbonylamino, (cycloalkyl(alkylcarbonylamino, arylcarbonylamino, aralkylcarbonylamino, (heterocycloalkyl)carbonylamino, (heterocycloalkyl)alkylcarbonylamino, heteroarylcarbonylamino, heteroaralkylcarbonylamino, alkoxycarbonylaminoalkylamino, (heteroaryl)arylcarbonylaminoalkylamino, heteroaralkylcarbonylaminoalkylamino, (heteroaryl)arylsulfonylaminoalkylcarbonylaminoalkylamino, arylsulfonylaminoalkylamino, alkoxycarbonyl, alkylcarbonyloxy, urea, thiourea, sulfamoyl, sulfamide, or carbamoyl; m is selected from 0, 1, 2, 3, or 4; provided that when m≧2, two adjacent R¹ groups can join together to form a 4- to 8-membered optionally substituted cyclic moiety; n is selected from 0, 1, 2, or 3; provided that when n≧2, two adjacent R² groups can join together to form a 4- to 8-membered optionally substituted cyclic moiety; and each of R^(x) and R^(y) is independently selected from hydrogen, alkyl, alkenyl, alkynyl, alkoxy, acyl, halo, hydroxy, amino, nitro, cyano, guanadino, amidino, carboxy, sulfo, mercapto, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, cycloalkylcarbonyl, (cycloalkyl)alkylcarbonyl, aroyl, aralkylcarbonyl, heterocycloalkylcarbonyl, (heterocycloalkyl)acyl, heteroaroyl, (heteroaryl)acyl, aminocarbonyl, alkylcarbonylamino, (amino)aminocarbonyl, alkylsulfonylaminocarbonyl, alkylsulfonylamino, cycloalkylcarbonylamino, cycloalkylsulfonylamino, (cycloalkyl)alkylcarbonylamino, (cycloalkyl)alkylsulfonylamino, arylcarbonylamino, arylsulfonylamino, aralkylcarbonylamino, aralkylsulfonylamino, (heterocycloalkyl)carbonylamino, (heterocycloalkyl)sulfonylamino, (heterocycloalkyl)alkylcarbonylamino, (heterocycloalkyl)alkylsulfonylamino, heteroarylcarbonylamino, heteroarylsulfonylamino, heteroaralkylcarbonylamino, heteroaralkylsulfonylamino, alkoxycarbonyl, alkylcarbonyloxy, urea, thiourea, sulfamoyl, sulfamide, carbamoyl, cycloalkyl, cycloalkyloxy, cycloalkylsulfanyl, (cycloalkyl)alkyl, (cycloalkyl)alkoxy, (cycloalkyl)alkylsulfanyl, heterocycloalkyl, heterocycloalkyloxy, heterocycloalkylsulfanyl, (heterocycloalkyl)alkyl, (heterocycloalkyl)alkoxy, (heterocycloalkyl)alkylsulfanyl, aryl, aryloxy, arylsulfanyl, aralkyl, aralkyloxy, aralkylsulfanyl, arylalkenyl, arylalkynyl, heteroaryl, heteroaryloxy, heteroarylsulfanyl, heteroaralkyl, (heteroaryl)alkoxy, or (heteroaryl)alkylsulfanyl; or a pharmaceutically acceptable salt or N-oxide thereof.
 2. The compound of claim 1, wherein each of X₁, X₂, and X₃ is CR^(x).
 3. The compound of claim 2, wherein each R^(x) is independently selected from hydrogen, unsubstituted alkyl, hydroxyalkyl, haloalkyl, aminoalkyl, aryloxyalkyl, heteroaralkyloxyalkyl, alkoxy, halo, hydroxy, carboxy, cyano, guanadino, amidino, amino, carboxy, (heteroaryl)acyl, alkoxycarbonyl, aminocarbonyl, alkylcarbonylamino, cycloalkylcarbonylamino, heteroarylcarbonylamino, (heterocycloalkyl)alkoxy, (heteroaryl)alkoxy, (heteroaryl)alkylsulfanyl, heterocycloalkyl, (heterocycloalkyl)alkyl, heteroaryl, or heteroaralkyl.
 4. The compound of claim 2, wherein each R^(x) is independently selected from hydrogen, unsubstituted alkyl, hydroxyalkyl, trifluoromethyl, alkoxy, halo, hydroxy, cyano, guanadino, amidino, —NH₂, —NH(unsubstituted alkyl), —NH(hydroxyalkyl), —NH(alkoxyalkyl), —NH(carboxyalkyl), —N(unsubstituted alkyl)₂, —NH(heterocycloalkyl), —NH(heteroaryl), —NH(heterocycloalkylalkyl), —NH(aralkyl), —NH(heteroaralkyl), —NH—CO-alkyl, —NH—CO-heteroaryl, aminocarbonyl, heterocycloalkyl, or heteroaryl.
 5. The compound of claim 2, wherein each R^(x) is hydrogen, methyl, ethyl, —NH₂, —NH—CO-methyl, —NH—CO-ethyl, —NH—CO-pyridyl, or —CO—NH(OH).
 6. The compound of claim 2, wherein each of X₂, X₃, and X₄ is independently selected from —CH—, —C(CH₃)—, —C(OH)—, —C(NH₂)—, —C(CO—NH₂)—, —C(CO—NHOH)—, —C(NH(unsubstituted alkyl))-, —C(NH(aryl))-, —C(NH(aralkyl))-, —C(NH(heteroaryl))-, —C(NH(heteroarylalkyl))-, —C(NH—CO-(unsubstituted alkyl))-, —C(NH—CO-(aryl))-, —C(NH—CO-(heteroaryl))-, —C(NH—CO-(aralkyl))-, —C(NH—CO-(heteroarylalkyl))-, —C(NH—SO₂-(unsubstituted alkyl))-, —C(NH—SO₂-(aryl))-, —C(NH—SO₂-heteroaryl))-, —C(NH—SO₂-(aralkyl))-, —C(NH—SO₂-(heteroarylalkyl))-, —C(NH—SO₂—NH(unsubstituted alkyl))-, —C(NH—SO₂—NH(aryl))-, —C(NH—SO₂—NH(heteroaryl))-, —C(NH—SO₂—NH(aralkyl))-, —C(NH—SO₂—NH(heteroarylalkyl))-, —C(hydroxyalkyl)-, or —C(carboxy)-, and X₁ is —CH—.
 7. The compound of claim 2, wherein each of X₁ and X₂ is —CH—; X₄ is N; and X₃ is —C(NH₂)—, —C(NH(unsubstituted alkyl))-, —C(NH(aryl))-, —C(NH(aralkyl))-, —C(NH(heteroaryl))-, —C(NH(heteroarylalkyl))-, —C(NH—CO-(unsubstituted alkyl))-, —C(NH—CO-(aryl))-, —C(NH—CO-(heteroaryl))-, —C(NH—CO-(aralkyl))-, —C(NH—CO-(heteroarylalkyl))-, —C(NH—SO₂-(unsubstituted alkyl))-, —C(NH—SO₂—(aryl))-, —C(NH—SO₂-heteroaryl))-, —C(NH—SO₂-(aralkyl))-, —C(NH—SO₂-(heteroarylalkyl))-, —C(NH—SO₂—NH(unsubstituted alkyl))-, —C(NH—SO₂—NH(aryl))-, —C(NH—SO₂—NH(heteroaryl))-, —C(NH—SO₂—NH(aralkyl))-, or —C(NH—SO₂—NH(heteroarylalkyl))-.
 8. The compound of claim 2, wherein m is selected from 0, 1, or
 2. 9. The compound of claim 8, wherein each R¹ is independently selected from unsubstituted alkyl, hydroxyalkyl, haloalkyl, aminoalkyl, aryloxyalkyl, heteroaralkyloxyalkyl, unsubstituted alkenyl, alkoxy, acyl, halo, hydroxy, carboxy, cyano, guanadino, amidino, amino, carboxy, mercapto, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, aminocarbonyl, alkylcarbonylamino, alkoxycarbonyl, alkylcarbonyloxy, alkylsulfonyl, sulfamoyl, cycloalkyl, heterocycloalkyl, (heterocycloalkyl)alkyl, heteroaryl, or heteroaralkyl.
 10. The compound of claim 8, wherein m is 1 and R¹ is selected from 6-alkyl, 6-alkenyl, 6-cycloalkyl, or 6-halo.
 11. The compound of claim 8, wherein both Y₁ and Y₂ are N.
 12. The compound of claim 11, wherein n is selected from 1 or 2 and each R² is independently selected from unsubstituted alkyl, hydroxyalkyl, haloalkyl, aminoalkyl, aryloxyalkyl, heteroaralkyloxyalkyl, alkoxy, acyl, halo, hydroxy, carboxy, cyano, guanadino, amidino, —NH₂, monoalkylamino, dialkylamino, monocycloalkylamino, monoheterocycloalkyl-amino, monoheteroaryl-amino, mono(heterocycloalkylalkyl)amino, mono (heteroaralkyl)amino, —N(alkyl)(cycloalkyl), mercapto, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, —CO—NH₂, —CO—NH(alkyl), —CO—N(alkyl)₂, —NH—CO-alkyl, —N(alkyl)-CO-alkyl, —CO₂-alkyl, —O—CO-alkyl, —SO₂—NH₂, —SO₂—NH(alkyl), —SO₂—N(alkyl)₂, —NH—SO₂-alkyl, —N(alkyl)-SO₂-alkyl, —NH—CO—NH(alkyl), —N(alkyl)-CO—NH(alkyl), —NH-alkyl-NH—CO-alkyl-heteroaryl, —NH-alkyl-NH—CO-aryl-heteroaryl, —NH-alkyl-NH—CO-alkyl-NH—SO₂-aryl-heteroaryl, —NH-alkyl-NH—SO₂-aryl, —NH—SO₂—NH(alkyl), —N(alkyl)-SO₂—NH(alkyl), heterocycloalkyl, or heteroaryl.
 13. The compound of claim 12, wherein R² is substituted at the 3-position with a group selected from guanadino, amidino, —NH₂, monoalkylamino, dialkylamino, monocycloalkylamino, monoheterocycloalkylamino, monoheteroarylamino, mono((heterocycloalkyl)alkyl)amino, mono(heteroaralkyl)amino, —NH—CO—NH(alkyl), —N(alkyl)-CO—NH(alkyl), —NH-alkyl-NH—CO-alkyl-heteroaryl, —NH-alkyl-NH—CO-aryl-heteroaryl, —NH-alkyl-NH—CO-alkyl-NH—SO₂-aryl-heteroaryl, —NH-alkyl-NH—SO₂-aryl, —NH—SO₂—NH(alkyl), —N(alkyl)-SO₂—NH(alkyl), heterocycloalkyl, or heteroaryl.
 14. The compound of claim 13, wherein m is 1 and R¹ is selected from 6-methyl, 6-ethyl, 6-propyl, 6-chloro, 6-trifluoromethyl, 6-vinyl, or 6-cyclopropyl.
 15. The compound of claim 1, wherein m is selected from 0, 1, or
 2. 16. The compound of claim 15, wherein R¹ is substituted at the 5-position or the 6-position.
 17. The compound of claim 16, wherein R¹ is C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkylthio, halo, amino, aminocarbonyl, or alkoxycarbonyl.
 18. The compound of claim 15, wherein each R¹ is independently selected from unsubstituted alkyl, hydroxyalkyl, haloalkyl, aminoalkyl, aryloxyalkyl, heteroaralkyloxyalkyl, unsubstituted alkenyl, alkoxy, acyl, halo, hydroxy, carboxy, cyano, guanadino, amidino, —NH₂, monoalkylamino, dialkylamino, monoheterocycloalkylamino, monoheteroarylamino, mono(heterocyclylalkyl)amino, mono(aralkyl)amino, mono(heteroaralkyl)amino, carboxy, mercapto, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, —CONH₂, —CONH(alkyl), —CO—N(alkyl)₂, —NH—CO-alkyl, —N(alkyl)-CO-alkyl, —CO₂-alkyl, —O—CO-alkyl, —SO₂—NH₂, —SO₂—NH(alkyl), —SO₂—N(alkyl)₂, cycloalkyl, heterocycloalkyl, or heteroaryl.
 19. The compound of claim 18, wherein m is 1 and R¹ is selected from 6-methyl, 6-ethyl, 6-propyl, 6-chloro, 6-trifluoromethyl, 6-ethyl, 6-vinyl, or 6-cyclopropyl.
 20. The compound of claim 1, wherein both Y₁ and Y₂ are N.
 21. The compound of claim 20, wherein n is selected from 1 or 2 and each R² is independently selected from unsubstituted alkyl, hydroxyalkyl, haloalkyl, aminoalkyl, aryloxyalkyl, heteroaralkyloxyalkyl, alkoxy, acyl, halo, hydroxy, carboxy, cyano, guanadino, amidino, —NH₂, monoalkylamino, dialkylamino, monocycloalkylamino, monoheterocycloalkylamino, monoheteroaryl-amino, mono(heterocycloalkylalkyl)-amino, mono(heteroaralkyl)amino, —N(alkyl)(cycloalkyl), mercapto, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, —CONH₂, —CONH(alkyl), —CO—N(alkyl)₂, —NH—CO-alkyl, —N(alkyl)-CO-alkyl, —CO₂-alkyl, —O—CO-alkyl, —SO₂—NH₂, —SO₂—NH(alkyl), —SO₂—N(alkyl)₂, —NH—SO₂-alkyl, —N(alkyl)-SO₂-alkyl, —NH—CO—NH(alkyl), —N(alkyl)-CO—NH(alkyl), —NH—SO₂—NH(alkyl), —N(alkyl)-SO₂—NH(alkyl), —NH-alkyl-NH—CO-alkyl-heteroaryl, —NH-alkyl-NH—CO-aryl-heteroaryl, —NH-alkyl-NH—CO-alkyl-NH—SO₂-aryl-heteroaryl, —NH-alkyl-NH—SO₂-aryl, heterocycloalkyl, or heteroaryl.
 22. The compound of claim 21, wherein n is 1 and each R² is independently selected from guanadino, amidino, —NH₂, monoalkylamino, dialkylamino, monocycloalkylamino, monoheterocycloalkylamino, monoheteroarylamino, mono((heterocycloalkyl)alkyl)amino, mono(heteroaralkyl)amino, —NH—CO—NH(alkyl), —N(alkyl)-CO—NH(alkyl), —NH—SO₂—NH(alkyl), —N(alkyl)-SO₂—NH(alkyl), —NH-alkyl-NH—CO-alkyl-heteroaryl, —NH-alkyl-NH—CO-aryl-heteroaryl, —NH-alkyl-NH—CO-alkyl-NH—SO₂-aryl-heteroaryl, —NH-alkyl-NH—SO₂-aryl, heterocycloalkyl, or heteroaryl.
 23. The compound of claim 22, wherein R² is substituted at the 3-position.
 24. The compound of claim 1, wherein each of X₂, X₃, and X₄ is independently selected from —CH—, —C(OH)—, —C(NH₂)—, —C(NH(unsubstituted alkyl))-, —C(NH(aryl))-, —C(NH(aralkyl))-, —C(NH(heteroaryl))-, —C(NH(heteroarylalkyl))-, —C(NH—CO-(unsubstituted alkyl))-, —C(NH—CO-(aryl))-, —C(NH—CO-(heteroaryl))-, —C(NH—CO-(aralkyl))-, —C(NH—CO-(heteroarylalkyl))-, —C(NH—SO₂-(unsubstituted alkyl))-, —C(NH—SO₂-(aryl))-, —C(NH—SO₂-(heteroaryl))-, —C(NH—SO₂-(aralkyl))-, —C(NH—SO₂-(heteroarylalkyl))-, —C(NH—SO₂—NH(unsubstituted alkyl))-, —C(NH—SO₂—NH(aryl))-, —C(NH—SO₂—NH(heteroaryl))-, —C(NH—SO₂—NH(aralkyl))-, —C(NH—SO₂—NH(heteroarylalkyl))-, —C(hydroxyalkyl)-, —C(carboxy)-, or N.
 25. The compound of claim 1, wherein X₁ is —CH—.
 26. The compound of claim 1, wherein X₁ is N.
 27. The compound of claim 1, wherein X₂ is N.
 28. The compound of claim 1, wherein X₃ is N.
 29. The compound of claim 1, wherein X₄ is N.
 30. The compound of claim 1, selected from (2-Methoxy-ethyl)-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; (3-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-propyl)-carbamic acid tert-butyl ester; (3-Imidazol-1-yl-propyl)-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; (4-Methoxy-benzyl)-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; [2-(6-Methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridin-6-yl]-methanol; 3-(2-Methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine; (4-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butyl)-carbamic acid tert-butyl ester; (4-Amino-benzyl)-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; (5-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-pentyl)-carbamic acid tert-butyl ester; [3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-6-yl]-methanol; [3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-7-yl]-methanol; [3-(2-Amino-pyrimidin-4-yl)-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-8-yl]-(2-morpholin-4-yl-ethyl)-amine; [3-(2-Amino-pyrimidin-4-yl)-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-8-yl]-(2-pyridin-2-yl-ethyl)-amine; [3-(2-Amino-pyrimidin-4-yl)-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-8-yl]-(2-pyridin-3-yl-ethyl)-amine; [3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-6-yl]-methanol; [3-(2-Amino-pyrimidin-4-yl)-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-8-yl]-(2-pyridin-4-yl-ethyl)-amine; [3-(2-Amino-pyrimidin-4-yl)-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-8-yl]-(3-morpholin-4-yl-propyl)-amine; [3-(4-Methyl-piperazin-1-yl)-propyl]-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; [3-(4-Methyl-piperidin-1-yl)-propyl]-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; [4-(2-Pyridin-2-yl-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-2-yl]-pyridin-3-ylmethyl-amine; {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-((R)-1-phenyl-ethyl)-amine; {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-((S)-1-phenyl-ethyl)-amine; {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(1H-tetrazol-5-yl)-amine; {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(2H-pyrazol-3-yl)-amine; {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(2-morpholin-4-yl-ethyl)-amine; {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(2-pyridin-2-yl-ethyl)-amine; {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(2-pyridin-3-yl-ethyl)-amine; {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(2-pyridin-4-yl-ethyl)-amine; {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(3-morpholin-4-yl-propyl)-amine; {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(3-piperidin-1-yl-propyl)-amine; {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-[1,3,4]thiadiazol-2-yl-amine; 2-(6-Methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine; 2-(6-Methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid methyl ester; 2-(6-Methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid ethyl ester; 2-(6-Methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-ylamine; {7,7-Dimethyl-8-[5-(4-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butylcarbamoyl)-pentyl]-2-oxo-4-trifluoromethyl-7,8-dihydro-2H-1-oxa-8-aza-anthracen-5-yl}-methanesulfonic acid; 2-(2,7-Difluoro-6-hydroxy-3-oxo-9,9a-dihydro-3H-xanthen-9-yl)-3,5,6-trifluoro-4-[(4-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butylcarbamoyl)-methylsulfanyl]-benzoic acid; 2-(6-Methyl-pyridin-2-yl)-3-(2-morpholin-4-yl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine; 2-(6-Methyl-pyridin-2-yl)-3-(2-piperidin-1-yl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine; 2-(6-Methyl-pyridin-2-yl)-3-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine; 2-(6-Methyl-pyridin-2-yl)-3-[2-(1H-tetrazol-5-yl)-pyrimidin-4-yl]-imidazo[1,2-a]pyridine; 2-(6-Methyl-pyridin-2-yl)-3-pyrimidin-4-yl-imidazo[1,2-a]pyridine; 2-(6-Methyl-pyridin-2-yl)-3-pyrimidin-4-yl-imidazo[1,2-a]pyrimidin-7-ylamine; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-8-ylamine; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carbonitrile; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid ([1,4]dioxan-2-ylmethyl)-amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid ([1,4]dioxan-2-ylmethyl)-amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid (2-dimethylamino-ethyl)-amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid (2-methoxy-ethyl)-amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid (2-thiophen-2-yl-ethyl)-amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid [3-(4-methyl-piperazin-1-yl)-propyl]-amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid cyclopropylamide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid ethylamide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid hydroxyamide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid methoxy-amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid methyl ester; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid ([1,4]dioxan-2-ylmethyl)-amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid (2-amino-ethyl)-amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid (2-dimethylamino-ethyl)-amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid (2-hydroxy-ethyl)-amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid (2-oxo-2-pyridin-3-yl-ethyl)-amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid (2-thiophen-2-yl-ethyl)-amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid (piperidin-3-ylmethyl)-amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid 2,2-dimethylhydrazide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid cyclopropylamide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid ethyl ester; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid ethylamide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid hydroxyamide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid methoxy-amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-ylamine; 3-(2-Azetidin-1-yl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine; 3-(2-Methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid ethyl ester; 3-(2-Methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid methyl ester; 3-(2-Methanesulfonyl-pyrimidin-4-yl)-7-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine; 3-(2-Methanesulfonyl-pyrimidin-4-yl)-8-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine; 3,3-Dimethyl-N-[2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-yl]-butyramide; 3-(2-Methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carbonitrile; 3-(2-Methylsulfanyl-pyrimidin-4-yl)-2-pyridin-2-yl-imidazo[1,2-a]pyridine; 3,6-Dichloro-N-(4-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butyl)-2-(2,4,5,7-Tetrachloro-6-hydroxy-3-oxo-9,9a-dihydro-3H-xanthen-9-yl)-terephthalamic acid; 3-[2-(2-Methyl-aziridin-1-yl)-pyrimidin-4-yl]-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine; 3-[2-(4-Methyl-piperazin-1-yl)-pyrimidin-4-yl]-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine; 3-{[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carbonyl]-amino}-propionic acid methyl ester; 3-{[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carbonyl]-amino}-propionic acid methyl ester; 3-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-phenol; 4-(2-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-ethyl)-benzenesulfonamide; 4-(2-Pyridin-2-yl-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-2-ylamine; 4-[2-(6-Chloro-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 4-[2-(6-Methyl-pyridin-2-yl)-7-trifluoromethyl-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidine-2-carbonitrile; 4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidine-2-carboxylic acid amide; 4-[6-Bromo-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 4-[6-Chloro-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 4-[6-Fluoro-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 4-[6-Methyl-2-(6-methyl-pyridin-2-yl)-8-(2-morpholin-4-yl-ethylamino)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ol; 4-[6-Methyl-2-(6-methyl-pyridin-2-yl)-8-(2-pyridin-2-yl-ethylamino)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ol; 4-[6-Methyl-2-(6-methyl-pyridin-2-yl)-8-(2-pyridin-3-yl-ethylamino)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ol; 4-[6-Methyl-2-(6-methyl-pyridin-2-yl)-8-(2-pyridin-4-yl-ethylamino)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ol; 4-[6-Methyl-2-(6-methyl-pyridin-2-yl)-8-morpholin-4-yl-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ol; 4-[6-Methyl-2-(6-methyl-pyridin-2-yl)-8-morpholin-4-yl-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 4-[6-Methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 4-[7-Aminomethyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 4-[7-Methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 4-[8-Benzyloxy-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ol; 4-[8-Benzyloxy-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 4-[8-Bromo-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ol; 4-[8-Methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 6-Chloro-3-(2-methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine; 5-Dimethylamino-naphthalene-1-sulfonic acid (4-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butyl)-amide; 6-(2,7-Difluoro-6-hydroxy-3-oxo-3H-xanthen-9-yl)-N-(4-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butyl)-isophthalamic acid; 6-Amino-9-[2-carboxy-5-(4-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butylcarbamoyl)-phenyl]-xanthen-3-ylidene-ammonium; 6-Bromo-2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine; 6-Fluoro-2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine; 7-Amino-4-methyl-3-[(4-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butylcarbamoyl)-methyl]-2-oxo-2H-chromene-6-sulfonic acid; Cyclobutyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; Cyclopentyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; Cyclopropyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; Cyclopropyl-methyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; Dimethyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; Isopropyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; Methyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; N-(2-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-ethyl)-acetamide; N-(4-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butyl)-acetamide; N,N-Dimethyl-N′-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-ethane-1,2-diamine; N-[2-(6-Methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-yl]-3-pyridin-3-yl-propionamide; N-[2-(6-Methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-yl]-nicotinamide; N-[2-(6-Methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyrimidin-7-yl]-propionamide; N-[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carbonyl]-methanesulfonamide; N-[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carbonyl]-methanesulfonamide; N-[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-2-(3-methoxy-phenyl)-acetamide; N-[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-3,3-dimethyl-butyramide; N-[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-3-pyridin-3-yl-propionamide; N-[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-acetamide; N-[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-nicotinamide; N-[3-(2-Methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-2-(3-methoxy-phenyl)-acetamide; N-[3-(2-Methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-3,3-dimethyl-butyramide; N-[3-(2-Methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-3-pyridin-3-yl-propionamide; N-[3-(2-Methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-nicotinamide; N-[3-(2-Methanesulfonyl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-propionamide; N-[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-propionamide; N-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-acetamide; N1-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-butane-1,4-diamine; N1-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-propane-1,3-diamine; N-(4-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butyl)-(BODIPY FL) amide; N-(4-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butyl)-(Texas Red-X) amide; or pharmaceutically acceptable salts or N-oxides thereof.
 31. The compound of claim 1, selected from (2-Methoxy-ethyl)-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; (3-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-propyl)-carbamic acid tert-butyl ester; (3-Imidazol-1-yl-propyl)-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; (4-Amino-benzyl)-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; (5-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-pentyl)-carbamic acid tert-butyl ester; [3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-6-yl]-methanol; [3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-7-yl]-methanol; [3-(2-Amino-pyrimidin-4-yl)-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-8-yl]-(2-pyridin-2-yl-ethyl)-amine; [3-(4-Methyl-piperazin-1-yl)-propyl]-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; [3-(4-Methyl-piperidin-1-yl)-propyl]-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(2H-pyrazol-3-yl)-amine; {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(2-morpholin-4-yl-ethyl)-amine; {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(2-pyridin-2-yl-ethyl)-amine; {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(2-pyridin-3-yl-ethyl)-amine; {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(2-pyridin-4-yl-ethyl)-amine; {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(3-morpholin-4-yl-propyl)-amine; {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(3-piperidin-1-yl-propyl)-amine; {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-[1,3,4]thiadiazol-2-yl-amine; 2-(6-Methyl-pyridin-2-yl)-3-pyrimidin-4-yl-imidazo[1,2-a]pyrimidin-7-ylamine; 3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carbonitrile; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid (2-methoxy-ethyl)-amide; 3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid cyclopropylamide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid ethyl amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid hydroxyamide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid methoxy-amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid (2-thiophen-2-yl-ethyl)-amide; 3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid cyclopropylamide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid ethyl amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid methoxy-amide; 3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-ylamine; 3-(2-Azetidin-1-yl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine; 3-[2-(2-Methyl-aziridin-1-yl)-pyrimidin-4-yl]-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine; 3-{[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carbonyl]-amino}-propionic acid methyl ester; 4-(2-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-ethyl)-benzenesulfonamide; 4-[2-(6-Chloro-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidine-2-carbonitrile; 4-[6-Bromo-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 4-[6-Chloro-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 4-[6-Fluoro-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 4-[6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 4-[7-aminomethyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 4-[7-Methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 4-[8-Methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 6-(2,7-Difluoro-6-hydroxy-3-oxo-3H-xanthen-9-yl)-N-(4-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butyl)-isophthalamic acid; 7-Amino-4-methyl-3-[(4-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butylcarbamoyl)-methyl]-2-oxo-2H-chromene-6-sulfonic acid; Cyclobutyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; Cyclopentyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; Cyclopropyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; Cyclopropyl-methyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; Dimethyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; Isopropyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; Methyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; N-(2-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-ethyl)-acetamide; N-(4-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butyl)-acetamide; N-[3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-2-(3-methoxy-phenyl)-acetamide; N-[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-3,3-dimethyl-butyramide; N-[3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-3-pyridin-3-yl-propionamide; N-[3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-acetamide; N-[3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-nicotinamide; N-[3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-propionamide; N-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-acetamide; N1-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-butane-1,4-diamine; (4-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butyl)-carbamic acid tert-butyl ester; [3-(2-Amino-pyrimidin-4-yl)-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-8-yl]-(2-morpholin-4-yl-ethyl)-amine; [3-(2-Amino-pyrimidin-4-yl)-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-8-yl]-(2-pyridin-3-yl-ethyl)-amine; [3-(2-Amino-pyrimidin-4-yl)-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-8-yl]-(2-pyridin-4-yl-ethyl)-amine; [3-(2-Amino-pyrimidin-4-yl)-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-8-yl]-(3-morpholin-4-yl-propyl)-amine; [4-(2-Pyridin-2-yl-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-2-yl]-pyridin-3-ylmethyl-amine; {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-((R)-1-phenyl-ethyl)-amine; {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-((S)-1-phenyl-ethyl)-amine; {4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(1H-tetrazol-5-yl)-amine; {7,7-Dimethyl-8-[5-(4-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butylcarbamoyl)-pentyl]-2-oxo-4-trifluoromethyl-7,8-dihydro-2H-1-oxa-8-aza-anthracen-5-yl}-methanesulfonic acid; 2-(6-Methyl-pyridin-2-yl)-3-(2-morpholin-4-yl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine; 2-(6-Methyl-pyridin-2-yl)-3-(2-piperidin-1-yl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine; 2-(6-Methyl-pyridin-2-yl)-3-(2-pyrrolidin-1-yl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine; 2-(6-Methyl-pyridin-2-yl)-3-pyrimidin-4-yl-imidazo[1,2-a]pyridine; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-8-ylamine; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid ([1,4]dioxan-2-ylmethyl)-amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid ([1,4]dioxan-2-ylmethyl)-amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid (2-dimethylamino-ethyl)-amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid (2-thiophen-2-yl-ethyl)-amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid methyl ester; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid ([1,4]dioxan-2-ylmethyl)-amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid (2-dimethylamino-ethyl)-amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid (2-hydroxy-ethyl)-amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid (2-oxo-2-pyridin-3-yl-ethyl)-amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid (piperidin-3-ylmethyl)-amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid ethyl ester; 3-(2-Methylsulfanyl-pyrimidin-4-yl)-2-pyridin-2-yl-imidazo[1,2-a]pyridine; 3-[2-(4-Methyl-piperazin-1-yl)-pyrimidin-4-yl]-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine; 3-{[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carbonyl]-amino}-propionic acid methyl ester; 4-(2-Pyridin-2-yl-imidazo[1,2-a]pyridin-3-yl)-pyrimidin-2-ylamine; 4-[2-(6-Methyl-pyridin-2-yl)-7-trifluoromethyl-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidine-2-carboxylic acid amide; 4-[6-Methyl-2-(6-methyl-pyridin-2-yl)-8-(2-morpholin-4-yl-ethylamino)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ol; 4-[6-Methyl-2-(6-methyl-pyridin-2-yl)-8-morpholin-4-yl-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 4-[8-Benzyloxy-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ol; 4-[8-Benzyloxy-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 4-[8-Bromo-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ol; 5-Dimethylamino-naphthalene-1-sulfonic acid (4-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butyl)-amide; 6-Amino-9-[2-carboxy-5-(4-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butylcarbamoyl)-phenyl]-xanthen-3-ylidene-ammonium; 6-Bromo-2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine; 6-Fluoro-2-(6-methyl-pyridin-2-yl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-imidazo[1,2-a]pyridine; N,N-Dimethyl-N′-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-ethane-1,2-diamine; N1-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-propane-1,3-diamine; N-(4-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butyl)-(BODIPY FL) amide; N-(4-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butyl)-(Texas Red-X) amide; or pharmaceutically acceptable salts or N-oxides thereof.
 32. The compound of claim 1, selected from (2-Methoxy-ethyl)-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; (3-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-propyl)-carbamic acid tert-butyl ester; (3-Imidazol-1-yl-propyl)-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; (4-Amino-benzyl)-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; (5-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-pentyl)-carbamic acid tert-butyl ester; [3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-6-yl]-methanol; [3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-7-yl]-methanol; [3-(2-Amino-pyrimidin-4-yl)-6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-8-yl]-(2-pyridin-2-yl-ethyl)-amine; [3-(4-Methyl-piperazin-1-yl)-propyl]-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; [3-(4-Methyl-piperidin-1-yl)-propyl]-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(2H-pyrazol-3-yl)-amine; {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(2-morpholin-4-yl-ethyl)-amine; {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(2-pyridin-2-yl-ethyl)-amine; {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(2-pyridin-3-yl-ethyl)-amine; {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(2-pyridin-4-yl-ethyl)-amine; {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(3-morpholin-4-yl-propyl)-amine; {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-(3-piperidin-1-yl-propyl)-amine; {4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-[1,3,4]thiadiazol-2-yl-amine; 2-(6-Methyl-pyridin-2-yl)-3-pyrimidin-4-yl-imidazo[1,2-a]pyrimidin-7-ylamine; 3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carbonitrile; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid (2-methoxy-ethyl)-amide; 3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid cyclopropylamide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid ethylamide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid hydroxyamide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-6-carboxylic acid methoxy-amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid (2-thiophen-2-yl-ethyl)-amide; 3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid cyclopropylamide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid ethyl amide; 3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carboxylic acid methoxy-amide; 3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-ylamine; 3-(2-Azetidin-1-yl-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine; 3-[2-(2-Methyl-aziridin-1-yl)-pyrimidin-4-yl]-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine; 3-{[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridine-7-carbonyl]-amino}-propionic acid methyl ester; 4-(2-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-ethyl)-benzenesulfonamide; 4-[2-(6-Chloro-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidine-2-carbonitrile; 4-[6-Bromo-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 4-[6-Chloro-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 4-[6-Fluoro-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 4-[6-methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 4-[7-aminomethyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 4-[7-Methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 4-[8-Methyl-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamine; 6-(2,7-Difluoro-6-hydroxy-3-oxo-3H-xanthen-9-yl)-N-(4-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butyl)-isophthalamic acid; 7-Amino-4-methyl-3-[(4-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butylcarbamoyl)-methyl]-2-oxo-2H-chromene-6-sulfonic acid; Cyclobutyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; Cyclopentyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; Cyclopropyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; Cyclopropyl-methyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; Dimethyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; Isopropyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; Methyl-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-amine; N-(2-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-ethyl)-acetamide; N-(4-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-ylamino}-butyl)-acetamide; N-[3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-2-(3-methoxy-phenyl)-acetamide; N-[3-(2-Amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-3,3-dimethyl-butyramide; N-[3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-3-pyridin-3-yl-propionamide; N-[3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-acetamide; N-[3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-nicotinamide; N-[3-(2-amino-pyrimidin-4-yl)-2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyrimidin-7-yl]-propionamide; N-{4-[2-(6-methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-acetamide; N1-{4-[2-(6-Methyl-pyridin-2-yl)-imidazo[1,2-a]pyridin-3-yl]-pyrimidin-2-yl}-butane-1,4-diamine; or pharmaceutically acceptable salts or N-oxides thereof.
 33. A pharmaceutical composition comprising at least one compound of claim 1 and a pharmaceutically acceptable carrier.
 34. A pharmaceutical composition comprising at least one compound of claim 30 and a pharmaceutically acceptable carrier.
 35. A method of inhibiting the TGFβ signaling pathway in a subject, the method comprising administering to said subject an effective amount of at least one compound of claim
 1. 36. A method of inhibiting the TGFβ signaling pathway in a subject, the method comprising administering to said subject an effective amount of at least one compound of claim
 30. 37. A method of inhibiting the TGFβ type I receptor in a cell, the method comprising contacting said cell with an effective amount of at least one compound of claim
 1. 38. A method of inhibiting the TGFβ type I receptor in a cell, the method comprising contacting said cell with an effective amount of at least one compound of claim
 30. 39. A method of reducing the accumulation of excess extracellular matrix induced by TGFβ in a subject, the method comprising administering to said subject an effective amount of at least one compound of claim
 1. 40. A method of reducing the accumulation of excess extracellular matrix induced by TGFβ in a subject, the method comprising administering to said subject an effective amount of at least one compound of claim
 30. 41. A method of treating or preventing a fibrotic condition in a subject, the method comprising administering to said subject an effective amount of at least one compound of claim
 1. 42. A method of treating or preventing a fibrotic condition in a subject, the method comprising administering to said subject an effective amount of at least one compound of claim
 30. 43. The method of claim 41 or 42, wherein the fibrotic condition is selected from scleroderma, lupus nephritis, connective tissue disease, wound healing, surgical scarring, spinal cord injury, CNS scarring, acute lung injury, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, adult respiratory distress syndrome, acute lung injury, drug-induced lung injury, glomerulonephritis, diabetic nephropathy, hypertension-induced nephropathy, hepatic or biliary fibrosis, liver cirrhosis, renal fibrosis, primary biliary cirrhosis, fatty liver disease, primary sclerosing cholangitis, restenosis, cardiac fibrosis, opthalmic scarring, fibrosclerosis, fibrotic cancers, fibroids, fibroma, fibroadenomas, fibrosarcomas, transplant arteriopathy, radiation therapy-induced fibrosis, chemotherapy-induced fibrosis, and keloid.
 44. A method of inhibiting metastasis of tumor cells in a subject, the method comprising administering to said subject an effective amount of at least one compound of claim
 1. 45. A method of inhibiting metastasis of tumor cells in a subject, the method comprising administering to said subject an effective amount of at least one compound of claim
 30. 46. A method of treating a disease or disorder mediated by an overexpression of TGFβ, the method comprising administering to a subject in need of such treatment an effective amount of at least one compound of claim
 1. 47. A method of treating a disease or disorder mediated by an overexpression of TGFβ, the method comprising administering to a subject in need of such treatment an effective amount of at least one compound of claim
 30. 48. The method of claim 46 or 47, said disease or disorder being selected from the group consisting of demyelination of neurons in multiple sclerosis, Alzheimer's disease, cerebral angiopathy, squamous cell carcinomas, multiple myeloma, melanoma, glioma, glioblastomas, leukemia, and carcinomas of the lung, breast, ovary, cervix, liver, biliary tract, gastrointestinal tract, pancreas, prostate, and head and neck. 